SNPMiner Trials by Shray Alag


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Report for Mutation H63D

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 24 clinical trials

Clinical Trials


1 Hemochromatosis and Iron Overload Screening Study (HEIRS)

To determine the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis, in a multi-center, multiethnic, primary care-based sample of 100,000 adults. The study is conducted by the Division of Epidemiology and Clinical Applications of the NHLBI, the Division of Blood Diseases and Resources of the NHLBI, and the Ethical, Legal, and Social Implications (ELSI) Research Program of the NHGRI.

NCT00005541 Blood Disease Hemochromatosis Iron Overload
MeSH:Hematologic Diseases Hemochromatosis Iron Overload
HPO:Abnormality of blood and blood-forming tissues

Evidence suggests that early diagnosis and treatment can prevent disease manifestations and enable normal life expectancy The discovery of the HFE C282Y and H63D variants in the HLA gene region on chromosome 6 provides an opportunity for early and rapid genetic identification of individuals at risk for development of hereditary hemochromatosis. --- C282Y --- --- H63D ---

In order to obtain data on the prevalence of genetic factors in a routine care population, a random subgroup of approximately 20-40 percent of the 101,000 screenees will be genotyped for known variants, such as HFE C282Y and H63D, related to iron metabolism and overload. --- C282Y --- --- H63D ---


2 Studies of Phlebotomy Therapy in Hereditary Hemochromatosis

This study will evaluate the effectiveness of a test called MCV in guiding phlebotomy (blood drawing) therapy in patients with hemochromatosis an inherited disorder that causes too much iron to be absorbed by the intestine. The excess damages body tissues, most severely in the liver, heart, pancreas and joints. Because iron is carried in the hemoglobin of red blood cells, removing blood can effectively lower the body s iron stores. Patients with hemochromatosis undergo weekly phlebotomy treatments (1 pint per session) to deplete iron stores. This usually requires 10 to 50 treatments, after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron. A test that measures ferritin a protein involved in storing iron is commonly used to guide phlebotomy therapy in hemochromatosis patients. This study will compare the usefulness of the ferritin test with that of MCV, which measures red blood cell size, in guiding phlebotomy therapy. In addition, the study will 1) examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients, and 2) design a system for making blood collected from hemochromatosis donors available for transfusion into other patients. Patients 15 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study. Candidates will have a history, physical evaluation, review of medical records and blood tests, and complete a symptoms questionnaire. Participants will have the following procedures: - Phlebotomy therapy every 1 to 2 weeks, depending on iron levels - Blood sample collection for blood cell counts and iron studies at every phlebotomy session - Blood sample collection (about 2 tablespoons) every 1 to 2 weeks after iron stores have been depleted - Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron With each blood donation that will be made available for transfusion to other patients, participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors. These include screening for the HIV and hepatitis viruses and for syphilis. Patients who meet height and weight requirements may be asked to consider "double red cell" donations using apheresis. In this procedure, whole blood is collected through a needle placed in an arm vein, similar to routine phlebotomy. The blood then circulates through a machine that separates it into its components. The red cells are removed and the rest of the blood is returned to the body, either through the same needle or through a second needle in the other arm. Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service. Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy. If cirrhosis is found, the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved. Patients with arthritis will be offered evaluation by the NIH Arthritis Service and, depending on symptoms, may be advised to have X-ray studies or a joint biopsy.

NCT00007150 Hemochromatosis Procedure: Phlebotomy
MeSH:Hemochromatosis

- INCLUSION CRITERIA: Confirmed diagnosis of HH, defined by the following HFE genotypes: C282Y/C282 or C282Y/H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Description: Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion

Measure: MCV drops 1-3% below baseline

Time: 4 to 12 months after starting phlebotomy therapy

3 Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

This study will evaluate the effectiveness of pioglitazone, a new diabetes medicine, on decreasing insulin resistance and improving liver disease in patients with nonalcoholic steatohepatitis (NASH). NASH is a chronic liver disease with unknown cause that involves fat accumulation and inflammation in the liver, leading to liver cirrhosis in 10 to 15 percent of patients and significant liver scarring in another 30 percent. Although similar to a condition that affects people who drink excessive amounts of alcohol, NASH occurs in people who drink only minimal or no alcohol. It is most often seen in patients with insulin resistance. Pioglitazone decreases insulin resistance and improves blood lipid (fat) levels, so that it may improve liver disease in NASH. Patients with NASH 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history and physical examination and routine blood tests. They will see a dietitian for counseling on diet and weight reduction, if needed. They will stop taking any medications for liver disease and take a daily multivitamin pill. After 2 months, those eligible for participation will be enrolled in the study. Participants will be admitted to the Clinical Center for 2 to 3 days for a complete medical history, physical examination, blood tests, urinalysis, chest X-ray, electrocardiogram, abdominal ultrasound and a liver biopsy. After the diagnosis of NASH is confirmed, the following procedures will be performed: - Echocardiography - imaging test using sound waves shows the heart structure and function - Resting metabolic rate - measures amount of oxygen (and calories) used to maintain body functions at rest. While lying down, the patient wears a clear plastic hood over the head for 20 minutes while the amount of oxygen used is measured. - Magnetic resonance imaging (MRI) scans - shows the size of the liver and other organs. The patient lies on a table in a metal cylinder that contains a magnetic field (the scanner) for no more than 30 minutes while the organs are imaged. - Dual energy X-ray absorptiometry (DEXA) scan measures whole body composition, including amount of fat. The patient lies under an X-ray scanning machine for about 2 minutes. - Oral glucose tolerance test (OGTT) - measures blood sugar and insulin levels. The patient drinks a very sweet drink containing glucose (sugar), after which blood samples are collected at various intervals during the 3-hour test. The blood is drawn through a catheter (thin plastic tube) placed in the arm before the test begins. - Intravenous glucose tolerance test (IVGTT) - determines how the tissues respond to insulin and glucose. Glucose is injected into a vein, followed by a short infusion of insulin. Blood samples are collected through a catheter at various intervals during the 3-hour test. When the above procedures are completed, patients start taking pioglitazone by mouth once a day for 48 weeks, keeping track of the medication and any side effects. They will be seen at the clinic every 2 weeks for the first month and then every 4 weeks for the rest of the treatment period. The visits will include an interview and examination by a physician and blood draw for laboratory tests. Female patients will have a pregnancy test at each clinic visit. At the end of the treatment period patients will be admitted to the Clinical Center for a repeat medical evaluation that will include the procedures described above.

NCT00013598 Fatty Liver Nonalcoholic Steatohepatitis Drug: Pioglitazone
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---


4 Long-Term Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging. In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH. ...

NCT00062764 Hepatitis Drug: Actos (Pioglitazone)
MeSH:Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis Hepatitis

Hemochromatosis as defined by presence of 3+ or 4 iron on liver biopsy stain and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Description: A histological response was defined as a reduction in the NASH activity index by 3 points or more with improvements of at least 1 point each in steatosis, parenchymal inflammation, and hepatocellular injury.

Measure: Number of Patients With Improvement in Liver Histology

Time: 48 weeks

Secondary Outcomes

Measure: Number of Patients With Impaired Glucose Tolerance After Treatment

Time: 48 weeks

Measure: Mean Increase of Insulin Sensitivity Index

Time: 48 weeks

Measure: Average Increase in Weight After Treatment

Time: 48 weeks

Measure: Mean BMI Change

Time: 48 weeks

5 Treatment of Nonalcoholic Steatohepatitis With Metformin

Nonalcoholic Steatohepatitis (NASH) is associated with progressive liver disease, fibrosis, and cirrhosis. Although the cause of NASH is unknown, it is often associated with obesity, type 2 diabetes, and insulin resistance. At present, there are no approved treatments for NASH patients, but an experimental approach has focused on improving their insulin sensitivity. Metformin is one of the most commonly used medications for the treatment of diabetes. The purpose of this study is to determine whether the medical problems of NASH patients, specifically liver damage, improves when their insulin sensitivity is enhanced with metformin. The study will last 3 to 5 years and will enroll up to 30 patients. Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.

NCT00063232 Hepatitis Drug: Metformin
MeSH:Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis Hepatitis

7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Description: Patients under went liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint is a three point improvement in the histological NASH activity index with a decrease in at least two of the component scores and no worsening of fibrosis or increase in Mallory bodies.

Measure: Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)

Time: from baseline to 48 Weeks

Secondary Outcomes

Description: Alanine transaminase <42 U/L is considered normal

Measure: Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)

Time: from baseline to 48 weeks

Description: HOMA-IR is calculated from Fasting Glucose and Fasting Insulin

Measure: Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline

Time: from baseline to 48 weeks

6 Characterization of Cardiac Function in Subjects With Hereditary Hemochromatosis Who Are New York Heart Association Functional Class I

This study will examine the effect of iron buildup in the hearts of patients with hereditary hemochromatosis (HH), a genetic disease that causes the body to accumulate excess amounts of iron. The excess iron can damage the heart, liver, pancreas, skin, and joints. Generally, early treatment with phlebotomy (periodic removal of a unit of blood), and in some cases chelation (using a drug to remove iron from the body) slows down organ damage in HH patients. This study will try to elucidate the effect of iron buildup in the heart and determine if phlebotomy and chelation help keep the heart healthy. Patients with HH and healthy volunteers 21 years of age and older may be eligible for this study. (Normal volunteers will provide normal values of heart function that will be used to verify abnormalities detected in HH patients.) Patients must have a gene abnormality of Hfe gene Cys282Try homozygote. They may or may not be receiving treatment for HH and they must have no heart symptoms or serious organ damage due to HH. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), Holter EKG (24-hour EKG monitoring, see description below), and chest x-ray. Participants will undergo the following tests and procedures over 2 to 5 days: - Exercise test: The participant exercises on a treadmill while wearing a mouthpiece, which is used to measure how much oxygen is used. Electrodes placed on the chest and arms monitor the heartbeat during the test. - Echocardiography: This ultrasound test uses sound waves to take pictures. A small probe is held against the chest to allow a technician to take pictures of the heart and assess its function. A drug called Optison may be injected in an arm vein if needed to enhance the ultrasound images. - Exercise stress echocardiography: The participant exercises on a stationary bike while heart function is measured with an echocardiogram, EKG, and blood pressure cuff. - 24-hour Holter EKG: The participant wears a small machine that records heart rhythm continuously for 24 hours. The recorder is connected by cables to electrodes placed on the chest. - Magnetic resonance imaging: This test uses a magnetic field and radio waves to obtain detailed images of the heart and blood vessels. The participant lies flat on a table that slides inside the scanner, which is a large hollow tube. All tests are performed once in normal volunteers and in patients who have received standard treatment for HH. Untreated patients repeat the tests 6 months after beginning phlebotomy or chelation. Additional time points for these tests might be added if further evaluation is needed.

NCT00068159 Hereditary Hemochromatosis
MeSH:Hemochromatosis

No symptoms suggestive of heart disease or any other medical conditions, negative Hfe genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation. --- Cys282Tyr --- --- His63Asp ---

Primary Outcomes

Description: To assess detailed cardiac function using non-invasive cardiac imaging in Group A; untreated-NYHA Class I HH subjects without conventional therapy for HH, Group B; treated- NYHA Class I HH subjects with conventional phlebotomy and/or iron chelation therapy and compare these results to those from Group C; age-gender matched healthy control volunteers.

Measure: Echocardographic variable early diastolic peak tissue Doppler velocity of septal mitral annulus (Em).

Time: Baseline, 1, 2, and 5 years

Secondary Outcomes

Description: To compare the results of the cardiac functional abnormalities in HH to those from healthy control volunteers

Measure: Exercise testing variable change in ejection fraction in response to exercise

Time: Baseline only

7 A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Twice-Weekly Peginterferon Alpha 2a and Ribavirin Induction Therapy for Chronic Hepatitis C in Patients Who Are Coinfected With HIV-1

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus. HIV-infected patients 18 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2-1/2 year study. Candidates are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, the skin in the area over the biopsy site is numbed with a local anesthetic and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures: - Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV. - Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period. - Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy. - Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.

NCT00085917 Hepatitis C HIV Infections Drug: Double dose pegylated interferon with weight based Ribavirin Drug: standard dose pegylated interferon alfa -2a and ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

- Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y --- --- H63D ---

Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y --- --- H63D ---

Primary Outcomes

Description: SVR [ Sustained virological response] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.

Measure: Number of Participants With Sustained Virologic Response (SVR)

Time: 72 weeks

Secondary Outcomes

Description: normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L

Measure: Number of Participants With Normalization of Liver Enzymes

Time: week 24, week 48, week 72

Description: Adverse Events - Anemia, Neutropenia and Psychiatric adverse events

Measure: Number of Participants With Adverse Events

Time: 48 weeks

8 S-Adenosyl Methionine for Symptomatic Treatment of Primary Biliary Cirrhosis

This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury. Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale. Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe. After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.

NCT00125281 Liver Cirrhosis, Biliary Drug: S-adenosyl-methionine (SAMe) capsules
MeSH:Liver Cirrhosis Liver Cirrhosis, Biliary Fibrosis
HPO:Biliary cirrhosis Cirrhosis Hepatic fibrosis

Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---

Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than or equal to 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy.

Time: 12 weeks of therapy

Secondary Outcomes

Measure: Improvement in serum alanine aminotransferase and alkaline phosphatase.

Time: 12 weeks

9 Iron Depletion Therapy for Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.

NCT00230087 Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Procedure: blood donation
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus
HPO:Abnormality of the liver Decreased liver function Diabetes mellitus Elevated hepatic transaminase Hepatic steatosis

- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Inclusion Criteria - Histological evidence of NAFLD and enrollment in NASH CRN Database Study - Type 2 DM treated with diet or a stable dose of non-insulin sensitizing oral hypoglycemic agents for > 3 mo. --- C282Y --- --- H63D ---

- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in the United States. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method

Time: one year

Measure: (2) HOMA model- determined by the OGTT method

Time: one year

Secondary Outcomes

Measure: Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress

Time: one year

Measure: Changes in intrahepatic and intraabdominal fat content as determined by CT scan

Time: one year

Measure: Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2)

Time: one year

10 Effects of S-Adenosyl Methionine (SAMe) on Viral and Cell Signaling Response to Combination Therapy for Chronic Hepatitis C

This study will examine the effectiveness of S-adenosyl methionine (SAMe) in combination with peginterferon and ribavirin for treating hepatitis C virus. One out of three patients with hepatitis C develops cirrhosis of the liver, which can lead to liver failure or liver cancer. SAMe is a nutritional supplement that is made naturally in all cells of the body and acts to improve how the body handles stress. In laboratory experiments with liver cells, SAMe decreases the injury caused by liver toxins and improves the ability of interferon to block hepatitis C virus. Patients 18 years of age and older with hepatitis C infection who did not respond successfully to prior treatment with interferon and ribavirin or peginterferon and ribavirin may be eligible for this study. Participants receive the following treatment: - Peginterferon (given by injection) and ribavirin (taken by mouth) for 2 weeks - Washout period (no medications) for 4 weeks - SAMe (taken by mouth) for 2 weeks - Peginterferon, ribavirin and SAMe for 12-48 weeks, depending on patient response to treatment. Participants have a thorough physical evaluation before beginning treatment and again at the study's end. After starting treatment, patients return for clinic visits and blood tests weekly for the first several weeks, then less frequently (at 2-week, then 4-week and 8-week intervals until up to 72 weeks) to monitor symptoms, drug side effects, hepatitis C virus levels, liver enzyme levels and immune responses to hepatitis C. ...

NCT00475176 Chronic Hepatitis C Drug: Peginterferon alfa-2a Drug: Ribavirin Drug: S-adenosyl methionine for Chronic Liver Disease
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---

Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Description: Improvement of slopes of decline in hepatitis C virus Ribonucleic acid in second course compared with first course in days 7 to 14 of therapy

Measure: Improvement in Viral Kinetics During the First 2 Weeks of Therapy

Time: Days 7 to 14 of therapy

Secondary Outcomes

Description: 2-log decline in HCV RNA by week 12 (early virological response) and sustained eradication of HCV RNA (sustained virological response).

Measure: 2-log Decline in HCV RNA by Week 12 (Early Virological Response) and Sustained Eradication of HCV RNA (Sustained Virological Response).

Time: 12 weeks from start of therapy

11 An Open Label Non-Randomized Trial to Assess Safety and Tolerability of Alb-Interferon Alfa 2b Every Two Weeks With Ribavirin Among HIV/HCV Coinfected Individuals

This study will determine if Albumin-linked interferon (Albinterferon alfa-2b) every 2 weeks is safe and tolerated by patients infected by both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). This is a new medication developed for HCV. It may help the immune system fight infections, especially those caused by viruses. Albinterferon alfa-2b appears quite similar to other interferons, in side effects and action in controlling HCV. Patients ages 18 and older who are infected with HCV genotype 1, are HIV positive, are infected with HCV, and have evidence of HCV-induced liver disease; and who are not pregnant or breast feeding may be eligible for this study. Many visits to NIH over a 76-week period are required. There will be collection of blood and urine, pregnancy test, and tests of HCV in the blood. A liver biopsy is required before start of the study if patients have not had one within 1 year. Another is done at the end of 72 weeks. An eye exam is done before start of the study and repeated later. An optional procedure called automated pheresis is done at the study beginning. Researchers can study patients' immunity to control HCV. Blood is drawn through a needle in an arm vein and spun in a machine to separate the desired blood component. Remaining blood is returned to the patient. Patients will receive Albinterferon alfa-2b at a dose of 900 mcg every 2 weeks for 48 weeks, by injection under the skin. Ribavirin is given at 1,000 mg or 1,200 mg by mouth twice daily, depending on a patient's weight. Side effects of Albinterferon alfa-2b are fatigue, headache, joint and muscle pain, and sleeplessness. The major side effect of ribavirin is anemia. Visits ranging from week 3 to 44 will determine the safety of Albinterferon alfa-2b and ribavirin and to see effects on reducing the HCV viral load. For weeks 48, 52, 56, 64, 72, and 76, patients will return for a clinic visit and blood tests. At week 72, an abdominal ultrasound and liver biopsy are done. Week 76 includes discussion of biopsy results.

NCT00489385 HIV Infections HCV Drug: Albinterferon Drug: Ribavirin Drug: Albuferon
MeSH:HIV Infections

Those subjects with, or a history of previous phlebotomy for iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y --- --- H63D ---

Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Safety and tolerability of two doses of Albinterferon alpha 2b with ribavirin.

Secondary Outcomes

Measure: Histologic, virologic responses to Albinterferon alpha 2b and ribavirin

12 Therapeutic Effect of Erythrocyte Apheresis as Compared to Full Blood Phlebotomy in Patients With Hereditary Hemochromatosis

Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. The optimal treatment, therefore, is still a matter of discussion Prevention of organ damage has traditionally been accomplished by drawing of full blood (phlebotomy), which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective removal of red blood cells (red cell apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred. This study is a controlled trial in which participating patients are asked to be randomized to red cell apheresis or traditional phlebotomy. Each group will be followed by means of well-defined assessments in order to explore possible advantages and disadvantages of each method in order to establish what type of treatment should be recommended.

NCT00509652 Hemochromatosis Procedure: Arm 1: Erythrocyte apheresis Procedure: Arm 2: Whole blood phlebotomy
MeSH:Hemochromatosis

Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y --- --- H63D ---

- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y --- --- H63D ---

Exclusion Criteria: 1. Contra-indications to either treatment modality 2. Patients who are not able to co-operate 3. Lack of informed consent Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y --- --- H63D ---

Inclusion criteria 1. Diagnosis 1. Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y --- --- H63D ---

2. Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Decline in ferritin levels and transferrin saturation

Secondary Outcomes

Measure: Decline in hemoglobin levels

Measure: Patient discomfort during therapeutic procedure

Measure: Time consumption

Measure: Costs

13 Effect of Iron Depletion by Phlebotomy Plus Lifestyle Changes vs. Lifestyle Changes Alone on Liver Damage in Patients With Nonalcoholic Fatty Liver Disease With Increased Iron Stores

Patients will be randomized to lifestyle changes alone or lifestyle changes associated with iron depletion. Iron depletion will be achieved by removing 350 cc of blood every 10-15 days according to baseline hemoglobin values and venesection tolerance, until ferritin < 30 ng/ml and transferrin saturation < 25%. Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. Smaller phlebotomies (250 cc) will be allowed for carriers of beta-thalassaemia trait. Maintenance phlebotomies (as much as required) will then be instituted to keep iron stores depleted (ferritin < 50 ng/ml and transferrin saturation < 25%, MCV <85 fl). Before starting treatment, patients will undergo ECG, and in the presence of hyperglycemia or hypertension also echocardiography (see exclusion criteria). Change in diabetes medication dosage or start of new therapy will be allowed for HbA1C values <6% or ≥ 7%. According to accepted criteria, previously untreated patients should be treated with metformin. If possible, newly diagnosed hypertension should be treated with Ace-inhibitors.

NCT00658164 Nonalcoholic Fatty Liver Disease Other: Iron depletion treatment
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis

*Hemochromatosis, as defined by homozygosity for the C282Y HFE mutation or compound heterozygosity for C282Y/H63D mutations or Hepatic Iron Index ≥ 1.9. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: To determine in a 24 month controlled study whether iron depletion by phlebotomy improves insulin sensitivity, and thereby reduces hepatic steatosis and inflammation in subjects with nonalcoholic steatohepatitis

Time: 24 months

Secondary Outcomes

Measure: To assess the effect of iron depletion on glucose tolerance status. Glucose tolerance will be determined by OGTT in subjects without type 2 diabetes (T2D), and by HbA1c levels and the change in dosage of pharmacological therapy in those with T2D.

Time: 24 months

14 A Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Cancer Patients With Chemotherapy-Associated Anemia

RATIONALE: Darbepoetin alfa may cause the body to make more red blood cells. Red blood cells contain iron that is needed to carry oxygen to the tissues. It is not yet known whether giving darbepoetin alfa (DA) together with intravenous iron or oral iron is more effective than giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy. PURPOSE: This randomized phase III trial is studying giving darbepoetin alfa together with iron to see how well it works compared with giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy in patients with cancer.

NCT00661999 Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Biological: darbepoetin alfa Dietary Supplement: ferrous sulfate Drug: sodium ferric gluconate complex in sucrose Other: placebo
MeSH:Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders
HPO:Anemia Leukemia Lymphoma Lymphoproliferative disorder Multiple myeloma

DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y --- --- H63D ---

DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y --- --- H63D --- --- C282Y --- --- H63D ---

Primary Outcomes

Description: Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Measure: Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response

Time: 16 Weeks

Secondary Outcomes

Measure: Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL

Time: 16 Weeks

Measure: Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions

Time: Week 1 to Week 16

Description: Value at 7 weeks minus value at baseline.

Measure: Mean Increment in Hemoglobin Level at Week 7

Time: Baseline and 7 weeks

Description: Value at 16 weeks minus value at baseline.

Measure: Mean Increment in Hemoglobin Level at Week 16

Time: Baseline and 16 weeks

Description: Hematopoietic response was defined as Hb increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Measure: Time to Hematopoietic Response

Time: 16 weeks

Measure: Time to First Red Blood Cell (RBC) Transfusions

Time: 16 weeks

Description: Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.

Measure: Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)

Time: Baseline and 16 weeks

Description: SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study

Time: Baseline and 16 weeks

Description: Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study

Time: Baseline and 16 weeks

Description: FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study

Time: Baseline and 16 weeks

Measure: C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16

Time: 1 Week, 7 Weeks and 16 Weeks

Measure: Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16

Time: 1 week, 7 weeks and 16 weeks

Measure: Ferritin Level at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

Description: MCV is a measure of the average red blood cell volume.

Measure: Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

Measure: Transferrin Saturation at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

15 A Phase II Trial of the Safety and Efficacy of Iron Reduction by Phlebotomy in Recipients of Hematopoietic Stem Cell Transplants

Hypothesis: The reduction of total body iron by phlebotomy will be safe and feasible in the post-HSCT setting Iron overload is common after hematopoietic stem cell transplantation. It is associated with chronic liver disease, with increased rates of infection and decreased survival. Eligible, consenting patients will have once monthly phlebotomy procedures (500ml) for 12 months. SAFETY: At each visit, patients will have a comprehensive assessment prior to starting and after completing the phlebotomy. This assessment will include determination of pain at phlebotomy site, local infection and an assessment of symptoms of anemia including presyncope, fatigue and dyspnea. The patient's pulse, blood pressure, respiratory rate and temperature will also be determined before and following the phlebotomy. EFFICACY: Iron stores will be measured serially in each patient. Measurements will be performed prior to the start of phlebotomy, and at 6 months and 12 months following the start of the series of 12 phlebotomies. These evaluations will be undertaken regardless of the number of phlebotomies which the patient actually undergoes. Iron stores will be estimated by measuring serum ferritin and transferrin saturation levels. Total body iron will be estimated from hepatic and cardiac iron concentration as measured by magnetic resonance imaging (MRI). Gandon et al. (12) described a non-invasive technique using MRI to measure hepatic iron stores. Iron is a paramagnetic substance which causes local magnetic field inhomogeneities leading to dephasing and signal loss in MRI. Gradient echo sequences are most susceptible to their effects because they do not use a 180° refocusing pulse, unlike conventional spin-echo sequences. Gandon et al. used multiple gradient echo sequences, compared the signal in liver to adjacent muscle and used this ratio to correlate with hepatic iron levels measured on tissue biopsy samples using spectrophotometric analysis. Multiple sequences were used because the nomogram comparing the L/M signal ratio is linear over only a small concentration of tissue iron.

NCT00689182 Iron Iron Overload Procedure: monthly phlebotomy x 12 months
MeSH:Iron Overload

Serum samples will also be collected at baseline to screen for the most common mutations of the HFE gene (C282Y mutation and H63D mutation) as hereditary hemochromatosis is common in the general population and may contribute to iron overload in HSCT recipients. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Iron stores, total body iron

Time: 1 year

16 The Effect of the Dietary Supplement Protandim on Non-Alcoholic Steatohepatitis: A Randomized, Double Blind, Placebo-Controlled Study

The purpose of this study is to evaluate the effect of Protandim on the degree of liver injury after one year of supplementation. Protandim is a nutritional supplement composed of the following 5 botanical extracts: Bacopa Moniera extract, Milk Thistle extract, Ashwagandha powder, Green tea, and Turmeric extract. Protandim is commercially available and can be purchased without a prescription. Our findings could lead to a better understanding of the role of oxidative stress and antioxidant therapy in NASH and may ultimately help improve patient care. Hypothesis #1: Protandim will lead to a significant improvement in NAS compared to placebo. Hypothesis #2: Protandim will lead to a significant decrease in serum markers of oxidative stress and liver chemistry tests. Hypothesis #3: Protandim will lead to decreased levels of TNF- α compared to placebo.

NCT00977730 Non-Alcoholic Steatohepatitis Dietary Supplement: Protandim Dietary Supplement: Placebo
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

7. Iron overload/hemochromatosis, as defined by the following: elevated transferrin saturation (greater than 45 percent) OR serum ferritin (> 300 microg/L in men or >200 microg/L in women), with one of the following: 1) presence of 3+ or 4+ stainable iron on liver biopsy (if obtained); or 2) Hemochromatosis gene testing showing homozygosity for C282Y or compound heterozygosity for C282Y/H63D (if obtained). --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Change in NAS at study completion in the Protandim group compared to the placebo group.

Time: 12 months

17 Impact of Host Iron Status and Iron Supplement Use on Growth and Viability of the Erythrocytic Stage of Plasmodium Falciparum

The purpose of this study is to perform laboratory based studies to determine if the growth and development of the malaria parasite is effected by iron status of its host (the person infected with the malaria parasite). Iron deficiency affects over 500 million people including many pregnant women and children from areas of the world that are plagued by malaria. Some population based studies have suggested that iron deficiency protects people from getting malaria and this has raised questions about the wisdom of public health policies that provide universal iron supplementation in countries where malaria is common. We will use red blood cells and sera from patients with iron deficiency anemia, hereditary hemochromatosis and normal individuals who are taking iron supplements to look at this question in a very systematic way. This study should provide information for or against a possible mechanism by which iron deficiency may affect the malaria parasite. The results will contribute to efforts to develop evidence-based public health policies on iron supplementation policies in malaria-endemic areas. There are three different types of individuals involved in this study (1) people with iron deficiency anemia who will be taking iron supplementation (2) people without iron deficiency anemia who will be taking iron supplementation and (3) people with a condition called hereditary hemochromatosis who have an excess of iron in their bodies.

NCT01027663 Iron Deficiency Anemia Malaria Dietary Supplement: Iron Supplement
MeSH:Malaria Anemia, Iron-Deficiency
HPO:Iron deficiency anemia

From the genotype standpoint, only patients homozygous for the C282Y and H63D mutations and those that are compound heterozygotes for C282Y/H63D will be enrolled. --- C282Y --- --- H63D ---

From the genotype standpoint, only patients homozygous for the C282Y and H63D mutations and those that are compound heterozygotes for C282Y/H63D will be enrolled. --- C282Y --- --- H63D --- --- H63D ---


18 Effects of Phlebotomy on Insulin Sensitivity in Insulin Resistance-associated Hepatic Iron Overload Patients

The purpose of this study is to evaluate efficacy of phlebotomy on insulin sensitivity as evaluated by euglycemic-hyperinsulinic clamp in insulin resistance-associated hepatic iron overload patients.

NCT01572818 Insulin Resistance Iron Overload Procedure: phlebotomy Behavioral: dietary and lifestyle counseling
MeSH:Insulin Resistance Iron Overload
HPO:Insulin resistance

Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y --- --- H63D ---

Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y --- --- H63D --- --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Glucose Infusion Rate by euglycemic-hyperinsulinic clamp

Time: 6 months

Secondary Outcomes

Measure: hepatic parameters

Time: 6 months

Description: IL-6, TNF alpha, CRP

Measure: inflammation markers

Time: 6 months

Description: adiponectin, PAI1, leptin

Measure: Adipokins markers

Time: 6 months

Measure: SHBG

Time: 6 months

Measure: HOMA-IR

Time: 6 months

Description: transaminase (ALT, AST), gamma GT

Measure: Hepatic iron overload (MRI)

Time: 6 months

Measure: Abdominal and sub-cutaneous fat surface (MRI)

Time: 6 months

Description: serum iron, ferritin, saturation of transferrin

Measure: iron parameters

Time: at 6 months

Description: HDL-c, LDL-c, triglycerides

Measure: lipid profile

Time: at 6 months

19 Ezetimibe Versus Placebo in the Treatment of Non-alcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. Nonalcoholic steatohepatitis (NASH) represents the more severe end of this spectrum and is characterized by steatosis, ballooning degeneration and lobular inflammation with or without fibrosis. The etiology of NASH is not completely understood, but it is often associated with obesity, type 2 diabetes, hyperlipidemia and insulin resistance. Lipotoxicity, insulin resistance and oxidative stress appear to be central to the pathogenesis of NASH. Currently, there is no FDA approved treatment for NAFLD/NASH. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. Ezetimibe is an LDL lowering agent that works through inhibition of the fat absorption from the small intestine. In this study, we propose to treat 50 patients with NASH with either Ezetimibe or placebo for 24 weeks. After an initial evaluation for insulin sensitivity, MRI liver fat distribution and liver biopsy, patients will receive either 10 mg/day of Ezetimibe or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of Ezetimibe and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and liver biopsy. Pre and post treatment MRI-derived liver fat content, liver histology and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity, liver histology and liver biochemistry.

NCT01766713 Non Alcoholic Steatohepatitis Drug: Ezetimibe
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Change in Liver Fat as Measured by MRI-PDFF

Time: 24 weeks

20 Deferasirox Versus Venesection in Patients With Hemochromatosis and for Treatment of Transfusional Siderosis in Myelodysplastic Syndrome: Diagnostics and New Biomarkers.

Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC. Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment. Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.

NCT01892644 Hemochromatosis Myelodysplastic Syndromes Drug: Deferasirox Other: Venesection Drug: Deferasirox
MeSH:Preleukemia Myelodyspla Myelodysplastic Syndromes Hemochromatosis Iron Overload Syndrome
HPO:Myelodysplasia

The most common are the classic C282Y and H63D point mutations of the hemochromatosis protein HFE, which disturbs its interaction with the transferrin receptor 1, the first step in the hepcidin signal cascade. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Changes from baseline in liver iron concentration (LIC) and heart iron concentration (HIC) determined by Magnetic Resonance Imaging (MRI), and in bone marrow iron content determined by microscopy after treatment with deferasirox.

Time: 0, 6 and 12 months

Secondary Outcomes

Measure: Change of hepcidin concentration in serum

Time: 0, 6 and 12 months

Measure: Change of non-transferrin bound iron (NTBI) concentration in serum

Time: 0, 6 and 12 months

Measure: Change of multiple trace metals in serum

Time: 0, 6 and 12 months

Measure: Change of intracellular signal molecules, mTOR, NFkB and stress sensor p53 in blood cells

Time: 0, 6 and 12 months

Description: Marker of oxidative DNA damage

Measure: Change of 8-oxodG in urine

Time: 0, 6 and 12 months

Description: Cu,Zn-Super Oxid Dismutase (SOD)is an antioxidant enzyme

Measure: Change of Cu,Zn-SOD activity in erythrocyte hemolysate

Time: 0, 6 and 12 months

Description: Serum analysis

Measure: Clinical chemistry: Na, K, Ca, Creatinine, creatinine kinase, CRP, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), lactate dehydrogenase (LD), albumin, bilirubin.

Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment

Description: Morning spot urine sample.

Measure: Urine routine test strip for detection of blood, protein, and nitrite

Time: 0,2,4,6,8 weeks and 3,4,5,6,7,8,9,10,11,12 months

Measure: Ferritin concentration in serum

Time: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment

Measure: Transferrin saturation in serum

Time: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment

Measure: HbA1c

Time: 0, 2,6,12 months

Measure: INR ( International normalized ratio)

Time: 0,2,6,12 months

Measure: Analysis of hemoglobin, reticulocytes, hematocrit, MCV, leukocyte count (total and differential), and platelets

Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment

Measure: Urine trace metals

Time: 0, 6 and 12 months

Measure: Bone marrow sample

Time: 0, 6 and 12 months

Other Outcomes

Measure: Pregnancy urin test (hCG)

Time: 0, 6 and 12 months, 5 weeks posttreatment

21 Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.

NCT01963845 Non-alcoholic Fatty Liver Disease Drug: Sitagliptin Drug: Placebo
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y --- --- H63D ---

Primary Outcomes

Description: Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.

Measure: Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF

Time: Baseline and 24 weeks

Secondary Outcomes

Description: AST, measured in IU/L at baseline and 24 weeks

Measure: AST, Aspartate Aminotransferase

Time: Baseline and 24 weeks

Description: ALT, measured in IU/L at baseline and 24 weeks

Measure: ALT, Alanine Aminotransferase

Time: Baseline and 24 weeks

Description: LDL, measured in mg/dL at baseline and 24 weeks

Measure: LDL, Low-density Lipoprotein

Time: Baseline and 24 weeks

Description: HOMA-IR, calculated as [(glucose (mg/dL) X insulin (mg/dL)) / 405 ] at baseline and 24 weeks

Measure: HOMA-IR, Homeostatic Model Assessment of Insulin Resistance

Time: Baseline and 24 weeks

22 Aramchol Versus Placebo in the Treatment of HIV-associated Nonalcoholic Fatty Liver Disease and Lipodystrophy: A Randomized, Double-blinded, Allocation-concealed, Placebo-controlled Clinical Trial

A subset of patients with NAFLD that have not been extensively studied are those infected with human immunodeficiency virus (HIV). Currently, there is no FDA approved treatment for NAFLD or NASH. Additionally, there have been no significant clinical trials for HIV patients with NAFLD and there are no approved treatment options. We plan to conduct a randomized, double-blinded, placebo-controlled clinical trial to examine the efficacy of 600 mg of Aramchol daily (including 200 mg tablet and 400 mg tablet) versus identical placebo given over 12 weeks to improve HIV-associated hepatic steatosis as measured by a validated and accurate magnetic resonance imaging (MRI)-based technique.

NCT02684591 Nonalcoholic Fatty Liver Disease HIV Drug: Aramchol Drug: Placebo
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Lipodystrophy
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis Lipodystrophy

Evidence of another form of liver disease: Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg), Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum, Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy, Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with rimary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis, Wilsons disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilsons disease Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D, Drug-induced liver disease as defined on the basis of typical exposure and history,Bile duct obstruction as shown by imaging studies. --- C282Y --- --- H63D ---

Primary Outcomes

Description: To examine the efficacy of aramchol at 600 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with HIV-associated NAFLD

Measure: Efficacy of Aramchol 600 mg vs. Placebo in Improving Hepatic Steatosis Assessed by Magnetic Resonance Imaging in Patients With HIV-associated NAFLD

Time: 12 weeks

Secondary Outcomes

Description: To examine the efficacy of two doses of aramchol: 200 mg/tablet and 400 mg/tablet / day orally daily versus placebo in improving serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with HIV-associated NAFLD

Measure: Efficacy of Aramchol 600 mg Orally Daily Versus Placebo in Improving Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels in Patients With HIV-associated NAFLD

Time: 12 Weeks

Other Outcomes

Description: To examine the efficacy of aramchol in improving imaging-based biomarkers associated with changes in NAFLD

Measure: Efficacy of Aramchol in Improving Imaging-based Biomarkers Associated With Changes in NAFLD

Time: 12 weeks

23 Iron Supplement Effect Over Immune System and Neurobehavioral Child Development.

Objective: To evaluate the effect of Iron supplement with two different amounts (one in the higher limit and another in the lower limit of the suggested amount) according to the presence of mutations in the HFE gene in the physical, immune and neurobehavioral development in the 6 to 12 moth toddlers. Methodology: Subjects: 340 toddlers coming from Paediatric Serves of Sant Joan Hospital. Methods: At 6 and 12 months it done clinical history, food registry, biochemist determinations: haemoglobin, iron, transferrin, ferritin, reactive C protein and immune response (IL4, IL10, IL6 IFN, IgA, IgM, IgG, IgE). Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. Mental, psychomotor and behavioual development (Bayley Scales of Infant Development 2on Edition: 1993). We evaluate the level of language and communication (MacArthur), regulation and sensory process (Infant Toddler Symptom Checklist), familiar and environment surroundings (Scale Health General Parental Stress Index).

NCT02690675 Neurodevelopmental Disorders Lactation Dietary Supplement: Iron fortified formula milk
MeSH:Neurodevelopmental Disorders

Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. --- C282Y --- --- H63D ---

Primary Outcomes

Measure: Mental and psychomotor development with BSID (Bayley Scale of Infant Development) at 12 months.

Time: 12 months

Secondary Outcomes

Measure: Height at 12 months measured in centimeters

Time: 12 months

Measure: Weight at 12 months measured in grams

Time: 12 months

Measure: Head circumference at 12 months measured in centimeters

Time: 12 months

Measure: Risk of infections at 12 months measured qualitatively from record of presence or not of various infections as bronchitis, rhinitis, otitis etc.

Time: 12 months

24 Effectiveness of Adaptation of the Dose of Iron Supplementation in Pregnancy on Maternal-child Health. Randomized Clinical Trial (ECLIPSES)

Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the hypotheses are that an iron supplementation adapted to values of hemoglobin at the start of the pregnancy will would be more effective in preventing iron deficiency, without increasing the risk of hemoconcentration by the end of pregnancy. This would be helped optimize mother-child health status. The aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. To accomplish this objective a Randomized Clinical Trial (RCT) triple-blinded was designed. The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum 1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum 2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. This study will be conducted in non-anemic pregnant women at early gestation stage, and their subsequent newborns. The data recollected to mothers will be: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children, the data collected will be: ultrasound fetal biometry, anthropometric measurements, and temperament development Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

NCT03196882 Anemia Ferropenic Risk of Hemoconcentration (Iron Levels Risk of Hemoconcentration (Iron Levels > Risk of Hemoconcentration (Iron Levels >130g/L) Drug: 40mg/day of iron Drug: 20mg/day of iron Drug: 80mg/day of iron
MeSH:Anemia Anemia, Iron-Deficiency
HPO:Anemia Iron deficiency anemia

In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). --- C282Y --- --- H63D ---

Presence or absence of polymorphisms: C282Y and H63D. --- C282Y --- --- H63D ---

Units on a scale (score).. H63D polymorphisms of HFE gene. --- H63D ---

Primary Outcomes

Description: - Anemia is defined as Hb <110 g/L in the 1st and 3rd trimester, Hb <110 in 2nd trimester (Centers for Disease Control and Prevention, 1998).

Measure: Anemia

Time: at week 36 of gestation (3rd visit of study)

Description: - Ferropenic anemia is defined as: Hb < the normal limit, and serum ferritin (SF) <15 μg/L (WHO, 2007)

Measure: ferropenic anemia

Time: at week 36 of gestation (3rd visit of study)

Description: - Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).

Measure: Risk of hemoconcentration

Time: at week 36 of gestation (3rd visit of study)

Secondary Outcomes

Description: Presence or absence of polymorphisms: C282Y and H63D

Measure: C282Y polymorphisms of HFE gene

Time: Blood analysis at 12 weeks of gestation.

Description: weight (g)

Measure: Anthropometric parameters of newborn.

Time: At birth

Description: Units on a scale (score).

Measure: Neurorconductual development of newborn (Bayley Scales)

Time: 40days post-partum

Description: Presence or absence of polymorphisms: C282Y and H63D

Measure: H63D polymorphisms of HFE gene

Time: Blood analysis at 12 weeks of gestation.


HPO Nodes


HP:0001392: Abnormality of the liver
Genes 1390
SRD5A3 WHCR CSPP1 ATP7A IL2RG MYORG NR1H4 IL17RC PEX1 B9D1 CD40LG TCF4 INSR SKIV2L RRM2B TTC37 HPD PEX11B NEU1 DOCK6 RBPJ CLEC7A RNF43 PSAP HNF1B HSD3B7 VPS33A LIPT1 EFL1 SDHC CEP290 TGFB1 CHD7 TINF2 FOXP3 PRKCD ALG6 CR2 C11ORF95 PTPN3 LACC1 ABCB11 KRT8 PLEKHM1 SETBP1 CASK PEX10 PKLR HADHA GBA TINF2 SLC4A1 AGA HADHA RPS20 IL7R TCIRG1 FLI1 GLIS3 CFI UQCRC2 IL17RA DNASE1L3 TRNK MRPL3 LCAT MPV17 TBX1 PEX11B TMEM70 KLF1 INS HBB NDUFS1 KMT2E HFE FASTKD2 ALG9 CTRC KRT18 SOS1 EIF2AK3 WDR35 PYGL FASLG CORIN BSCL2 ALG8 CD81 TNFSF12 RHAG FAN1 NCF2 LMNB2 ACADM H19 FBP1 GNE TNFRSF1B ND3 RMRP XRCC2 PC SLC29A3 ACOX1 COG8 RHAG SLC30A10 CDKN2B TJP2 COX6B1 SMPD1 SPTB WDR60 CBS RPGRIP1 SRD5A3 RPGRIP1L MLH1 ATP8B1 TRIM37 TMEM67 NHP2 SLC11A2 INPP5E NFKB1 CDKN1A HADHA CA2 ACSF3 H19 POLD1 AP1S1 F5 LYRM4 SLC2A1 KRT6B PCK1 POLG2 SEC24C HNRNPA1 DHDDS ALG13 AKT2 APOA1 B3GLCT GBA MPC1 KRT16 TET2 LDLRAP1 SLCO2A1 ACVRL1 KCNH1 PIGS APC TMEM67 USP9X CAV1 IFT122 TNFSF11 LRPPRC POMC BBIP1 B9D2 PEPD ACAT1 LMNA SPTA1 ACVRL1 GATA6 LPL DIS3L2 GNPTAB PHKG2 TNFRSF1A IDUA KRIT1 SLC25A13 BMP2 GPI SNX10 AKR1D1 BBS1 MED25 APC MAN2B1 MTRR ALAS2 ERCC4 PEX14 PNPLA2 PIEZO1 MVK PEX16 BRCA2 BCS1L SBDS TUFM VPS13A IFT140 SDCCAG8 GBA AMACR PFKM HFE PTPN11 APC INSR NPC1 CTNS TSFM PEX5 IFT172 BRCA1 IFT80 ERCC4 SLC25A13 RFWD3 PSMB4 HBA2 WDR19 ALDOA ELN ATP8B1 JAK2 MPI SMPD1 HMBS TBX1 ABCA1 ICOS UROD DCTN4 DKC1 LIG4 NBAS PEX3 TRNE ACADVL SDHA GPC3 TREX1 PEX10 CAV1 MYC HADHB HGSNAT GBA MMUT PEX26 RAB27A PEX12 PMM2 RREB1 RPGRIP1L CLDN1 MPL UQCRB MRPS16 UGT1A1 WDPCP FANCC HJV PEX13 CARS2 AP1B1 GYS2 PROP1 MRPS7 PEX2 PEPD G6PC MCM4 MMUT COG4 ABCC2 PEX26 HLA-DRB1 PPARG NDUFS7 NPHP1 VIPAS39 ABHD5 SBDS PIGA APOA1 GP1BB EFL1 VCP SLC17A5 COX4I2 GPD1 GPC3 CA2 DDRGK1 NDUFAF1 COG5 PHKA2 TWNK PHKG2 KRAS CYBC1 USP18 TMEM231 SP110 PEX1 CIDEC EOGT MSH2 IL2RB SLC39A8 MEFV TANGO2 FERMT3 ATP7B PDGFRL ATM TTC21B TERT HMGCS2 HOXD13 ENG MYH9 CEL LONP1 FGA SLCO1B3 CYP27A1 MIF DPAGT1 TERT TF CLCN7 TMEM107 CD247 NDUFA6 TRAF3IP2 DNAJC19 APOB SMPD1 CEP290 PRDM16 STK11 ND2 LETM1 ITCH LPIN2 PEX6 CASR SLCO1B1 POLG TPP2 IFT172 ZAP70 CNTNAP2 SKI H19 CYP19A1 ABCG8 PKHD1 CC2D2A CTCF GCGR CD96 PIK3CA GAA PSAP LHX1 PEX2 UBE2T PSAP ND4 PEX6 SLC29A3 TACO1 RNASEH2B POLG2 ZMPSTE24 RELA TMEM67 PCK2 POMC CD79B LBR SRP54 AKR1D1 SLC39A4 SC5D RPGRIP1L PLPBP SPTA1 RERE NKX2-5 NDUFS4 FAH CC2D2A COX20 GATA6 TERT TRAPPC11 ARSA HBA1 FANCL RFX5 PEX14 HNF1A FUCA1 OCLN DCDC2 TPI1 GUCY2D PSAP NSD2 PIK3C2A STAT6 CEP19 TERC SF3B1 NDUFS6 COG6 ACADL HADH RRAS POU2AF1 NOD2 CLIP2 NDUFV1 ERCC8 PEX5 HBB NPHP3 CAVIN1 PSMB9 RFXAP TCF3 NRXN1 FECH CP GFM1 GYPC CTSC SLCO1B3 CD28 NOTCH2 GNS HAMP CDAN1 CEP120 C1QBP ADAR CEP290 POLG2 HBG2 TIMMDC1 PARN EIF2AK3 RHAG ALDOB TNFRSF13C IL21R TRMT10C RFXANK BMPR1A STX11 CD27 CASP8 DHCR7 SGSH SLC25A19 HNF1A CSPP1 BBS12 RFT1 NLRP3 USB1 TRIP13 TMEM67 IDUA PMS1 CPT2 SLC25A20 RFXAP ADA HSD3B7 RAG2 WDR35 RMRP PCSK1 PRSS1 KCNQ1 FDX2 NDUFS8 CEP290 ND1 CCDC115 NGLY1 LMNA WDR60 FANCA MSH6 TMPRSS6 POU6F2 IL2RG NCF1 NSD2 STEAP3 INTU ADAMTSL2 SON PIK3CA FANCM LDLR KCNJ11 CLDN1 DLD TNFSF11 ABCA1 PIEZO1 ARHGAP31 RBM8A SLC13A5 NOTCH2 PEX6 EPCAM MEN1 KRAS TRIM32 PEX14 DUOX2 PDGFRB HBB UBR1 PEX13 RAG1 ABCC2 CIDEC TBX19 SDHA APC ARL6 XIAP RASGRP1 TCIRG1 SMAD4 NHLRC2 ALG1 BRCA2 POU1F1 ND5 DLL4 NDUFB11 TNFRSF11A HLA-B GTF2I EPB42 CTRC SLC22A5 PEX1 IL2RA RNU4ATAC SLC37A4 BCS1L BCHE KCNJ11 LMNA TFR2 TREX1 GUSB BTNL2 TRAF3IP1 SLX4 TNFRSF13B CYBA UGT1A1 DNAJB11 KCNN3 DKC1 PEX3 VPS45 APOE SCO1 GPR35 TBX1 CR2 ATP6 PRKCD JAK2 CTNNB1 HESX1 NPHP1 LMNA APOE FANCI LYST TET2 PEX13 TP53 NUBPL TRAF3IP1 CCDC47 PDX1 TANGO2 TTC8 LYST AP1B1 RNASEH2A MUC5B IL17F SERPINA1 PEX6 FAN1 PKLR NPHP3 C1S NPHP4 FBN1 UGT1A1 KRT18 CYP7B1 CIITA GPC3 HADH HJV KPTN XYLT1 PEX16 CYP7B1 APC UGT1A1 CPT1A BBS5 PALLD CTC1 NSMCE2 FADD TTC7A BCS1L FARSB DDRGK1 NPHP3 IFNGR1 CFTR PEX16 XRCC4 FGFR2 HNF4A MPV17 GALT SLC25A1 ACADM ALG9 KLF11 MLH3 CLCN7 IGLL1 UGT1A1 CLPB GBA TALDO1 KRT8 BTD ARSA PLAGL1 HK1 ALG2 DPM2 C8ORF37 DMD SLC40A1 SLC26A4 G6PD GALK1 AGPAT2 PEX5 PDGFRA SLC40A1 IL2RG IYD KLF1 WT1 BBS10 ATP7A RNASEH2C SRP54 ABCC8 PEX13 DYNC2H1 SLC20A2 ESCO2 GPC4 PAX8 CLCA4 C4B PCCB COG8 ABCB4 XK TNFSF15 APPL1 HEXB CPT2 PEX6 XPR1 CTSA IER3IP1 ACOX1 B2M TNFRSF1B YARS2 DCLRE1C HYMAI SCARB2 CD70 BSCL2 AHCY LYZ SPINK1 SOX10 IDUA ABCC8 GABRD WT1 FASLG ERCC6 FOXF1 STOX1 TBX19 CTBP1 DPM1 ATP8B1 PEX12 BSCL2 ENG UCP2 PKD2 RNU4ATAC FGFR2 SCYL1 COG7 DAXX MST1 PSMB8 BLVRA GPIHBP1 HADHA NELFA SURF1 TNFSF12 GPC4 SMAD4 PEX19 GNAS TRMU COX10 ALAS2 NAGA DOLK PEX2 NHP2 MCCC1 TRIM28 DHFR DNAJC21 CTSK SETBP1 PEX3 WDR19 NAB2 DPM3 RECQL4 MVK RFT1 LZTR1 G6PC3 ANK1 CDKN1C STN1 KRAS PALB2 SEMA4A EPB42 UFD1 NHP2 LIPE RIT1 RNASEH2A DCDC2 FGFRL1 HNRNPA2B1 STEAP3 PARS2 DNAJC21 LHX3 TG DCLRE1C HMGCL DIS3L2 FOS VPS33B TMEM199 BRCA2 RBCK1 HELLPAR NFKB2 CASR LMNA NOP10 SFTPA2 XRCC4 PAX4 JMJD1C RAF1 CD46 PALB2 RAG2 DGUOK COX8A ND3 CFTR FANCE ICOS RMND1 RFX6 NDUFS7 IL12A LIG4 KIF23 SCYL1 NDUFS2 HLA-DRB1 FAS NCF1 ARSB MKS1 SLC25A20 RAD51 EWSR1 ALMS1 GALE PEX26 TSC1 MMAA SLC4A1 KRT17 PAX8 ABCA1 PEX19 ZIC3 ADA2 EPB41 SERPINA1 CFTR NPHP3 MOGS FBP1 FANCD2 LBR TNPO3 SLC25A4 ATP11C LRP5 TSHR NEK1 CCND1 MET VHL ABCG8 IDUA TRMU WDR34 ABCB4 SPECC1L ERCC4 DYNC2H1 MKS1 GLB1 ASAH1 ATP6V1B2 SLC25A13 NEUROG3 ND1 TCIRG1 HSD17B4 CDKN1B LRP5 STK11 IL1RN COG1 NRAS ND6 GBA BTK AMACR ETFA ND2 PPARG FLT1 COMT DGUOK CD19 PRPS1 GBA HADHB POU1F1 DLD MKKS SEC63 TRMT5 TGFBR2 GBA HMGCL SLC4A1 HBB TRNS1 MRPL44 DDOST PCCA ABCB4 LIPA ABCD3 LIPE GATA2 BTK REST SUMF1 FUCA1 PEX3 AGGF1 PEX14 RAG1 UROS ANKS6 KCNN4 SDHD PTEN TREX1 TSHB APOC2 SLC2A1 GLB1 CDKN1B CPA1 ASL HMBS IL36RN KIT INPPL1 HYOU1 TRIM37 HPGD ELN PEX19 TGFB1 CBS CYP27A1 RAG2 TGFB1 PSAP MMUT COX10 COX15 KCNN4 CYBB HMOX1 H19-ICR NDUFA11 PLIN1 DYNC2LI1 NDUFAF2 TERC MAD2L2 NDUFB9 MSH6 KRAS CD3E FOXRED1 CD19 HBG2 TRNV PCCA HNF1A KIT WRAP53 GCLC C8ORF37 COX14 ACAD9 GNMT TREX1 ATP6AP1 RFC2 HNF4A CD3D SLC25A13 PEX12 TMEM67 TERC CTLA4 TRNN CDKN2A LMNA BCS1L IDS MET IL7R CDKN2C TSHR PLIN1 PET100 GPC1 CPT1A HNF1B NLRC4 BRCA1 PEX3 DPM3 JAM3 GNPTAB TRNW DLL4 JAK3 IFT140 MICOS13 DNAJC19 PNPLA2 PRF1 NAGA CEP55 SC5D PIGM PMM2 GALT BBS7 HLA-DRB1 ITK PRKCD NDUFAF4 BBS2 LIPA NGLY1 IDUA HAVCR2 IQCB1 MFN2 NOS3 SUMF1 BBS9 NDUFAF1 MYBPC3 SLC30A10 PEX26 PEX10 EPB41 KCNAB2 ACADVL GUSB CPT2 AGPAT2 HBB POLG ETFDH NRAS PEX16 GLRX5 LRRC8A COA8 OSTM1 LIMK1 NLRP3 TBL2 LZTFL1 FH CPOX CEP164 PNPLA6 SLC37A4 SPTB ABCB11 TWNK SFTPC ALDH7A1 INPP5E HBA1 ATPAF2 SHPK ICOS SLCO1B1 FCGR2A SPRTN FBXL4 MARS1 ALG11 TMEM67 KIAA0586 CPT2 IL7R NDUFS3 RASA2 ACAD9 AUH TKT ATP7B NSMCE2 RHBDF2 OFD1 CLCN7 IFIH1 JAK2 WT1 DZIP1L HIRA DPM2 PRKCSH GNE NCF2 SLC25A19 ARSA TFAM COX15 COG2 CEP83 SNX14 KCNH1 NEK8 BBS1 NDUFAF3 PSAP CD79A BRIP1 SEC63 ADAMTS13 ANTXR1 IGF2 FANCF PDGFRA BLNK ALG8 WDR19 PEX10 TMEM126B TPO TALDO1 FAS PDGFB CLCN7 DHCR7 BMPER IFT172 PCCB TP53 CTLA4 SDCCAG8 GCK NOTCH1 PTRH2 ADA NCF4 SLC35A2 SMAD4 STAT1 TTC37 GDF2 TMEM165 IL12RB1 RFXANK IRF5 NDUFAF5 TNFRSF13B PEX12 TRAPPC11 INVS CALR TRHR SPINK1 CD28 MECP2 SEC23B AGL ABCG8 CIITA WDR19 HBG1 GALNS OFD1 TMEM216 CC2D2A ABHD5 PEX2 LARS1 TTC21B GCDH RPGRIP1L STX1A IGF2R IGF2 BTK LIPA TRNL1 MKS1 COG2 SLC25A15 PKD1 CC2D2A TNFRSF13C SLC4A1 SP110 CASP10 ATRX PKHD1 PRKCSH HNF1B SKIV2L SOS2 KRT6A PIK3R1 TARS2 RRAS2 RTEL1 POLG TCTN2 CD55 GBE1 CCDC28B PRKAR1A SLC7A7 CYTB IFT27 NPC2 BSCL2 NDUFB10 COG4 SDHB SAA1 AP3D1 ITCH SLC5A5 PRSS1 SAR1B PEX11B RAG1 GDF2 ALMS1 F5 PMS2 COA8 GBA HBB TSC2 CASP10 CASR EXTL3 LETM1 NDUFS4 HAMP DYNC2LI1 TRIM28 PHKB PSMB8 RAD51C AKT2 ARVCF SH2D1A DUOXA2 ZAP70 LHX4 C15ORF41 RNU4ATAC POLR3A HNF4A AGA RNASEH2C TYMP IFT172 MYD88 JAG1 APOE LTBP3 ASAH1 NPM1 COG6 IKZF1 PHKA2 SLC7A7 CYBA HFE GLB1 NLRP1 CBL RFX5 MS4A1 HNF4A BBS4 ARSA NAGLU BTNL2 FAM111B PLEKHM1 DMPK AIRE BPGM MLXIPL FANCG EARS2 WDR35 SAMHD1 PGM1 AP1S1 AXIN1 LMNA ALDOB ADK PRSS2 KCNQ1OT1 HBA2 CAVIN1 BLK SNX10 PPARG RRM2B CYP7A1 IFT80 BAZ1B CTLA4 FAH SLC25A15 NEUROD1 PEX1 NDUFV2 PEX5 SLC22A5 MLH1 FANCB WDR34 CPLX1 IARS1 WDPCP EXTL3 TMEM216 TERT BOLA3 XIAP MYRF CTNNB1 CYBB SPTB GANAB NPHP3 NAGS CYC1 TTC7A NOP10 MSH2 APC UNC13D TRNW JAK2 MMEL1 MMAB IGHM MPI IFT43 MRAS NDUFB3 PCSK9 FAS STXBP2 ANK1 CFH PTPRC LBR SPIB VPS33A IL6 TET2 ASS1 NDUFA1 FECH ABCG5 MPL GTF2IRD1 PEX12 AP3B1 IFIH1 ETFB PEX19 PEX1 PRKAR1A ERBB3 A2ML1
Protein Mutations 4
C282Y G20210A H63D I148M
HP:0001903: Anemia
Genes 730
SRD5A3 NDUFS7 CTC1 KLF1 TBXAS1 SRP54 IL2RG TET2 RPS27 AMMECR1 SLC25A38 MLX CD40LG ERCC6L2 RPS24 YARS2 CFI DCLRE1C SCARB2 ALX4 UBE2T MPL TSR2 EXT2 MUC1 XRCC4 VPS33A FAM111A EFL1 WT1 FASLG TSR2 PNPO RPS29 SDHC BCL10 LAMC2 OCRL CHD7 TINF2 FOXP3 NT5C3A ENG PRKCD CR2 PLEKHM1 CASK IRAK1 DAXX MALT1 PKLR GBA TINF2 PSMB8 ZBTB20 SLC4A1 WFS1 NHEJ1 TACO1 RPL35A TCIRG1 FLI1 BMPR1A TNFSF12 CFI BMPR1A SMAD4 LAT ACVR1 COX10 ALAS2 MTRR FOXP1 LYRM7 DHFR TERT DNAJC21 RPL15 HBA1 CTSK KLF1 PGK1 HBB HBB CLCNKB RPS10 MTHFD1 FASTKD2 G6PC3 AASS BRCA1 ANK1 UROS EPB42 TEK FASLG SBDS NHP2 MYSM1 CD81 TNFSF12 RHAG CFH SMAD4 HBB LRBA NDUFS3 STEAP3 CDCA7 DNAJC21 CP DCLRE1C HMGCL RMRP XRCC2 RAG1 PGK1 F8 HELLPAR NFKB2 RECQL4 NPHP4 EPO RHAG COX6B1 REN COL7A1 SPTB RPL35 CD46 PALB2 RAG2 NDUFB8 SRD5A3 FTCD FCGR2A COX8A HPRT1 PTF1A WAS TBCE SPTA1 KDM6A FANCE ICOS SLC11A2 CLPX NFKB1 FCGR2B CA2 KIF23 HLA-DRB1 FAS ALAD RPL26 RAD51 EWSR1 MMAA SLC4A1 CAT NDUFS2 STAT3 SLC2A1 ADA2 EPB41 C1R APOA1 GBA ATRX FANCD2 TET2 UMPS SLCO2A1 ATP11C ACVRL1 KRT14 RTEL1 RPL5 ITGB3 GLA TMEM67 FANCC HBA2 DNMT3B HBA1 LAMA3 TNFSF11 BIRC3 SDHA RPS14 IFNG HAVCR2 IRF2BP2 RPS19 RPL35A PEPD TCIRG1 SPTA1 ACVRL1 GLA PIGA FANCL YARS2 STK11 NDUFA12 GPI SNX10 ECHS1 THRA RPL27 APC NDUFV2 ACD BCOR MTRR GBA ALAS2 ERCC4 PIEZO1 RPL26 HBG1 MVK AK1 STAT1 MTFMT CFB SBDS WAS NFKB1 AK2 IFT140 PFKM MMACHC RPS24 RNF113A HMGCL UMPS SLC4A1 HBB GATA1 BRCA1 TRNS1 PARN ZBTB24 STIM1 RFWD3 KIF15 PCCA HBA1 NDUFS2 ITGB4 PSMB4 DNASE1 HBA2 ABCD3 ALDOA RPS28 TET2 COL7A1 ACTN4 SMPD1 RPS17 ABCB7 ABCA1 ZBTB16 NUMA1 TINF2 DKC1 BMPR1A LIG4 RPS7 AGGF1 NDUFAF6 RAG1 UROS KCNN4 IREB2 NPHP1 RPL15 SLC2A1 FMO3 RPS27 RPS26 KIT ALPL HYOU1 STAT5B HPGD GBA C1QA TGFB1 SLX4 RAG2 TERC BMPR1A MMUT KCNN4 HMOX1 FANCB LAMA3 RPS28 SLC19A3 FANCA MPL STIM1 ELANE FANCC CD46 PET100 PGM3 SLC4A1 MAD2L2 ERCC2 EPHB4 KRAS FOXP3 RPS7 MMUT TGFB1 CD19 HBG2 KIT SARS2 SBDS WRAP53 GCLC COX14 EFL1 COX4I2 ORAI1 STING1 NABP1 CRIPT PUS1 CA2 FARS2 ERCC3 SLC19A2 WIPF1 SLC25A13 TERC DKC1 NSUN2 TRNN PHKG2 ETV6 NBN NDUFV1 STAT3 SP110 UBR1 PUS1 PRF1 RARA PHGDH IL2RB FERMT3 ATP7B RPL27 PET100 LCAT LAMB3 C3 COL7A1 HLA-B NLRC4 ENG CD59 COX15 NDUFA10 TERT TF TNFAIP3 LPIN2 MECOM PIGT DNAJC19 NDUFS1 PRF1 DNAJC19 GALT ITK PTEN PRKCD LIPA ABCD4 IDH1 STK11 RPL11 ATRX LPIN2 GATA1 NPM1 TPP2 SAMD9L ALAS2 KIF1B CD3G NDUFAF3 EPB41 ABCG8 SLC12A3 HBB POLG PRDX1 WFS1 NRAS CISD2 GLRX5 PRKAR1A LAMC2 COA8 OSTM1 RPS29 ATRX SCO2 NLRP3 SLC46A1 DGKE FIP1L1 MYSM1 UBE2T CPOX SLC29A3 LAMB3 TRNT1 TACO1 COL7A1 HBD SPTB NDUFA9 MTR PML GSS SMAD4 TRNT1 TBL1XR1 HBA1 SRP54 SHPK RPL18 SMARCAL1 SPTA1 ISCU DNM1L ELANE MARS1 IDH2 RPS26 GNA14 CAD IL7R COX20 GREM1 FANCE MMP1 HBA1 NDUFAF2 FANCL RFX5 NPHP1 ATP7B ATRX HBB HSPA9 CLCN7 JAK2 TPI1 MPIG6B SLC40A1 PSAP FOXRED1 LIG4 PHGDH SURF1 TERC FANCG SF3B1 KMT2D NOD2 BRIP1 SLC19A2 ADAMTS13 HBB RPL5 GATA1 NBN FANCF PDGFRA PSMB9 ALG8 FECH CP GYPC TALDO1 ABCB7 FAS PTH1R CLCN7 PCCB FAM111A HAMP CDAN1 PGM3 STIM1 DBH LMBRD1 ADA HBG2 GTF2E2 SMAD4 RPS17 STAT1 PARN RPS14 RFXANK RHAG TNFRSF13C TNFRSF13B STX11 CALR UROD ACAD8 NLRP3 PNP USB1 SEC23B RPL31 CIITA HBG1 RFXAP ADA LARS1 RAG2 RMRP COL4A1 FDX2 COQ2 PFKM COG1 CLCN7 BTK FANCA AMN NDUFA13 TF SEC61A1 NDUFS4 F2 SLC4A1 STEAP3 CASP10 ATRX GTF2H5 FANCM TARS1 KCNE1 RTEL1 SLC46A1 TNFSF11 ABCA1 CD55 PIEZO1 RBM8A ITGA2B CTLA4 PNPO SLC7A7 KCNQ1 RPS15A HELLS PLEC NDUFAF5 RPS10 SDHB ELMO2 HPRT1 HBB ANK1 MPLKIP ITGB4 RAG1 SAMD9L DDX41 IGH RAG1 SPTA1 IRX5 FANCD2 SDHA GDF2 COA8 GBA HBB TFRC RASGRP1 CASP10 TCIRG1 ADA2 NHLRC2 CASR COL7A1 PDHA1 BRCA2 PNP NPHP4 TNFRSF11A STAT4 RMRP PSMB8 RAD51C PCNT PLEC HBA2 HLA-B SH2D1A EPB42 SMARCD2 LARS2 ZAP70 RPL11 C15ORF41 SPTA1 IL2RA TCN2 PTPN22 SMARCAL1 TYMP MYD88 TFR2 GPX1 TREX1 SAMD9 BTNL2 PACS2 NDUFA4 SLX4 OPA1 GCLC NPM1 GATA1 COG6 IKZF1 PHKA2 ADAR SLC7A7 DKC1 NLRP1 MS4A1 VPS45 CFHR1 SCO1 RPS19 NDUFA2 PRKCD TMPRSS6 PLEKHM1 TP53 AIRE BPGM GATA1 FANCG RPS15A FANCI LYST TET2 TNFRSF4 CFHR3 MMP1 HBB SLC4A1 COL17A1 HBA2 LYST SNX10 HBB RRM2B CTLA4 PKLR IL12B PHF21A FERMT1 FANCB NDUFS8 SFXN4 HBB-LCR TERT GATA1 PRKACG XIAP SPP1 CUBN SPTB GSS CTC1 CCND1 TTC7A TTC7A NOP10 FARSB LIPT1 ABCB6 UNC13D IFNGR1 TRNW MMAB GATA1 PLA2G4A FAS HBB ANK1 CFH CLCN7 VPS33A SURF1 CBLIF TALDO1 AGXT HBA2 MMADHC HK1 GP1BA MAD2L2 ENG FECH G6PD TBXAS1 THBD TERT ERBB3
Protein Mutations 4
C282Y C677T H63D V617F
HP:0001871: Abnormality of blood and blood-forming tissues
Genes 1877
TCAP CTC1 KLKB1 TET2 RPS27 MYH9 SLC25A38 COL1A1 COL5A1 TCF4 RPS24 SERPINF2 ALX4 MPL TSR2 EXT2 EFL1 ATM CAP2 SDHC BCL10 OTULIN CD8A OCRL CHD7 FOXP3 PROS1 ASXL1 PRKCD PLEKHM1 SETBP1 FCGR2C GCDH MALT1 PKLR SERPINC1 THBD SLC4A1 ERAP1 FLI1 CYB5R3 F5 GGCX DNASE1L3 SUFU FOXP1 TGFB3 PIEZO1 VWF KLF1 PGK1 VPS13B LOX CTRC EGLN1 SOS1 GINS1 EIF2AK3 MECOM FASLG GP9 F2 TNFSF12 KIT LMNB2 NDUFS3 AEBP1 GNE XRCC2 SLC29A3 EPO COX6B1 SPTB VHL SGPL1 GNB1 SRD5A3 CBFB SPARC MLH1 AEBP1 EPHB2 TGFBR3 NHP2 CLPX NFKB1 FCGR2B F13B TRNS1 PTEN PTPN11 MPL PRLR NUTM1 STAT3 TEK SERPINF2 FBN1 STAT3 SSR4 FKTN TPMT SLC2A1 PARN NRAS VPS13A GBA SSR4 LEPR BLM ACVRL1 KRT14 ANKRD11 SH2B3 DNMT3B RAD54B IFNG RPS19 RPL35A HLA-DPA1 GUCY1A1 SDHB CXCR4 GPI ECHS1 AKR1D1 ACD MPL RUNX1 MAN2B1 ACSL4 HBG1 MVK PROS1 STAT1 FN1 JAK2 AMACR PFKM GP1BB KCNE5 GATA1 BRCA1 ZBTB24 RFWD3 PIK3R1 HBA1 NDUFS2 TGFB3 RPS28 COL4A2 COL7A1 JAK2 MPI SMPD1 RPS17 ABCA1 ICOS NUMA1 DKC1 LIG4 NBAS ITGB3 ND5 SDHD PEX3 SMAD4 BCL6 MYC STAT5B GBA LMAN1 PMM2 JAK2 NTHL1 FLNA STIM1 HOXA11 VHL MRPS7 EPHB4 MMUT TGFB1 BRCA2 F13A1 SCN5A SLC17A5 ORAI1 GFI1B NABP1 PUS1 SLC19A2 NSUN2 PHKG2 CYP2C9 NBN KRAS TXNRD2 STAT3 PEX1 SRC PRF1 EOGT PHGDH HLCS FERMT3 LAMB3 ATM COL7A1 MYH9 THPO NDUFA10 TERT TF MECOM PIGT NPM1 NDUFS1 ITGA2 KCNJ11 KIT SLC4A4 LPIN2 CASR TPP2 COL4A5 CD3G NDUFAF3 ABCG8 CASP10 CYB5R3 RBM10 SLC46A1 UBE2T TACO1 COL7A1 RNASEH2B NDUFA9 GSS SMAD4 F10 PSTPIP1 BCR CD79B RPL18 RPS26 IKBKG FAH COX20 GATA6 FANCE RIN2 ARF1 HBA1 KIF11 RFX5 NPHP1 CHD7 OCLN TPI1 MPIG6B GNAS CLPB PSAP FOXRED1 CARD9 PHGDH SLC35A1 CARD11 RRAS NOD2 APOB SDHC HTRA2 SLC19A2 BAG3 RIN2 LYST RPL5 GP9 TCF3 FECH CACNA1S HLA-B CIITA HAMP CDAN1 PROC CBL ADAR GTF2E2 PLG RPS17 PARN COL3A1 RFXANK BMPR1A STX11 TET2 GALC ADA2 HNF1A SH3GL1 TTI2 IL23R PMS1 FGG RFXAP COL4A1 FLNA PRF1 COG1 MTAP FANCA MSH6 AMN NDUFA13 COL5A2 SERPINC1 PRLR CD151 MYH7 TONSL GTF2H5 PIK3CA FANCM KCNE1 GGCX VHL ABCA1 CAPN3 PIEZO1 ARHGAP31 RBM8A PSEN1 CTLA4 RPS15A HELLS GFI1B EPCAM NF1 HPRT1 TRIP13 MPLKIP RAG1 MYLK RASGRP1 MLLT10 MTHFR PDHA1 F5 TNFRSF11A IL10RA PCNT HLA-B CTRC SMARCD2 PLOD3 SPTA1 PTPN22 SLC17A5 KCNJ11 F12 TFR2 TREX1 BTNL2 SLX4 TNFRSF13B OPA1 NEXN CYBA GATA1 ADAR DKC1 ARPC1B FGB VPS45 ALG12 SCO1 CR2 VWF SMAD3 GATA1 RPS15A APOE FANCI LYST TET2 STT3B ATOH7 ABCC9 HBG2 MMP1 RPSA HBB PDX1 JAK2 COL17A1 LYST HBB RNASEH2A PIK3CA C2 CIITA SFXN4 RET PEX16 HBB-LCR CYP7B1 BRD4 GNAS GSS A4GALT F13A1 TTC7A FLNA FARSB GATA1 KRT14 HNF4A MLH3 CLCN7 CLPB GDNF TAF1A GBA CBLIF ALG2 GATA2 ARL6IP6 G6PD TERT IL2RG KLF1 RNASEH2C SRP54 ABCC8 SLC20A2 CYP2A6 IGHM FOXN1 SLC2A1 TAZ TMPO NOTCH3 CYP4V2 SCARB2 CD70 SPINK1 MUC1 FAM111A RAB27A NOTCH1 DPM1 RAG2 LAMC2 PEX12 NT5C3A RNU4ATAC IRAK1 DAXX MST1 RAF1 NHEJ1 TNFSF12 GNAS TRMU KCNQ1 ALAS2 PDE4D CBL TCF4 NHP2 SLC39A13 CCM2 APC DLL4 TERT DNAJC21 UNC93B1 CTSK HBB RYR1 AKT1 FLNA MVK G6PC3 ANK1 TEK NHP2 ETV6 CFH RIT1 UNC119 HBB RAG1 STEAP3 PPCS CDCA7 IGH CCND1 DCLRE1C VPS33B PGK1 F8 LMNA TRNQ PAX4 COL7A1 MDM2 COX8A PTF1A WAS ABL1 KDM6A FANCE ICOS SDHD LIG4 KIF23 HLA-DRB1 FANCF TET2 TSC1 SLC4A1 NDUFS2 STT3B ADA2 TGFBR2 GFI1 CFTR FOXN1 FANCD2 FKBP14 ATP11C VHL GLA CDC42 TERT ARMC5 SLC25A11 MAP1B BIRC3 STXBP1 ASAH1 RFWD3 NAXD GLA TNFRSF13B FANCL YARS2 F7 THRA GBA AKT1 RPL27 PLOD1 FIBP FLT1 COMT MVK GBA KIT MTFMT CFB WAS NFKB2 AK2 TMTC3 TGFBR2 UMPS CDC42 SLC4A1 TRNS1 FADD PARN DDOST CHEK2 COX1 LIPA ANGPTL6 GCNT2 GATA2 ACTN4 ABCB7 ZBTB16 FUCA1 BMPR1A ND4 CAPN5 KCNN4 PTEN TREX1 SLC2A1 GLB1 RPS27 RPS26 PTPN22 HYOU1 HPGD C1QA TGFB1 CBS SLX4 RAG2 PICALM TERC MMUT KCNN4 HMOX1 ENG BUB3 RYR1 FANCA DYNC2LI1 ELANE PET100 TERC CCR1 MAD2L2 MPDU1 ERCC2 KRAS FOXP3 CD3E CD19 KIT HLA-DRB1 GCLC COX14 CSRP3 ACAD9 FLT3 CRIPT CEP57 TREX1 CD3D WIPF1 SLC25A13 PEX12 TERC BCL11B TRNN NDUFV1 BLNK PTPN11 IL7R PDGFRB RHOH F5 CTLA4 RARA GPC1 F13B HLA-B NUMA1 KRAS TNFAIP3 JAK3 EPAS1 NDP GALT ITK PRKCD ABCD4 IDH1 RUNX1 FOXE3 ATRX CLCN7 GATA1 NPM1 COL1A2 PEX26 TAZ ANKRD26 LAMTOR2 ELN EPB41 TCN2 SLC12A3 PRDX1 WFS1 NRAS CISD2 GLRX5 LRRC8A COA8 SH2B3 OSTM1 CEBPA KLF1 FIP1L1 CPOX TRNT1 CALR SPTB TBL1XR1 TERT IL2RG MDH2 MMADHC ICOS FBXL4 MARS1 TNNC1 RASA2 GREM1 VCL ACP2 MMP1 NDUFAF2 ATP7B TP53 HBB TGFBR1 CLCN7 SCN11A SOS1 HIRA DPM2 TFAM CCBE1 APP ELANE NUP214 KMT2D SEC63 ADAMTS13 BUB1B NBN FANCF CARD11 CD36 PLVAP FAS PTH1R PDGFB CLCN7 ADAMTS2 WAS PCCB HLA-DPB1 ARHGAP26 DLST PGM3 POLE ADA PANK2 GDF2 RFXANK CYP26C1 UROD SIK3 SEC23B RPL31 TP63 HBG1 DNMT3B NLRC4 BMPR2 COQ2 PFKM BTK NBEAL2 EPOR ITGB4 TBX2 NDUFS4 RASA1 MAT2A CASP10 ATRX PRKCSH F9 SOS2 PIK3R1 RRAS2 COL3A1 CHST14 HAX1 GNAQ PRDM5 SDHB PRKAR1A ITGA2B SLC7A7 CYTB KCNQ1 CDH23 SAA1 ATP6V1A RASGRP2 LBR KCNJ11 CD79A ATRX ANK1 ATM RNASEH2B PRSS1 ETHE1 TNXB SPTA1 RTEL1 IRX5 GDF2 PMS2 GBA HBB HBB TSC2 GP1BB ATR ADA2 CASR SGCG PNP ETHE1 NPHP4 TP53 PSMB8 RAD51C LARS2 CYP11B2 TCN2 KIT AGA SMARCAL1 MYD88 APOE TRAC NPM1 IKZF1 PHKA2 GNAQ GLB1 HPS3 NDUFA2 KRT5 GATA2 TMPRSS6 PLEKHM1 BAP1 TP53 TNXB PGM1 GATA2 LMNA IKBKG ALDOB TGFBR1 CTLA4 IL12B MAX PRDM16 MYD88 ZNF341 ABCC6 IDH1 NDUFS8 TERT GATA1 BCL10 SPP1 CYBB CUBN PTEN NBEAL2 CCND1 NOP10 GP1BA SDHB MSH2 PLEC ABCB6 GLB1 UNC13D TRNW CCM2 JAK2 MMAB RET SDHA IGHM FZD4 ANK1 CFH LBR TAL2 NF2 HOXA11 ANO6 MYH6 NIPBL HBA2 CISD2 TET2 DOCK8 MPL CYCS CREBBP ATP6V1E1 IFIH1 GP1BA THBD SPATA5 SRD5A3 NDUFS7 EPG5 TBXAS1 ATP7A IL2RG MYORG IDH2 FLT3 TGFB2 NR1H4 MLX HLCS CD40LG ERCC6L2 GATA1 TTC37 DNM2 CFI IVD UBE2T BRAF NEU1 DOCK6 RBPJ SERPIND1 RNF43 HSD3B7 VPS33A CTRC TSR2 TRNL1 PNPO PLEC TP53 TINF2 MCFD2 ALG6 CR2 DSE CASK PDCD10 CD3D GBA ACTN1 TINF2 ZBTB20 TACO1 RPS20 RPL35A ACTN2 IL7R TCIRG1 BMPR1A CFI BMPR1A LAT ACVR1 CHST14 ADA MTRR TBX1 PEX11B B2M ND1 EPO MAP2K2 NFIX SAMHD1 INS HBB COL1A2 AIP CLCNKB COL4A1 RPS10 MTHFD1 COX2 FASTKD2 AASS BRCA1 UROS PIK3CD CORIN SBDS CD81 RHAG NCF2 CP TNFRSF1B RMRP RECQL4 B4GALT1 COG8 NPHP4 RHAG BCL11B SLC30A10 SPINK5 SMPD1 REN RPL35 CBS UBE2A LMX1B NDUFB8 FTCD FGG SPTA1 LDB3 MEFV SLC11A2 CA2 PSEN2 ALAD RAG1 RPL26 DCLRE1C F5 FGA STAT3 TAZ CYB5A SEC24C TSC1 RAF1 ELANE ACTC1 C1R APOA1 NF1 AGK ATRX ADAMTS3 TET2 UMPS SLCO2A1 RTEL1 TMEM67 FANCC HBA1 ZNF469 TNFSF11 SDHA RPS14 HAVCR2 MSH2 WRAP53 PEPD ACAT1 SPTA1 ACVRL1 PIGA RS1 COL5A2 DOCK2 KRIT1 NDUFA12 SNX10 APC GP6 GATAD1 FGB FHL2 NDUFV2 BCOR MTRR ALAS2 ERCC4 PIEZO1 SBDS VPS13A NFKB1 SDHD IFT140 GBA PTPN11 TREM2 MMACHC NPC1 FZD4 PEX5 SH2B3 MAP2K1 ERCC4 STIM1 FIG4 LAMA4 ITGB4 GLI1 PSMB4 HPS1 DNASE1 HBA2 ALDOA MTTP TET2 LRP5 CALR SRSF2 RPS7 NDUFAF6 PEX10 NPHP1 RPL15 FMO3 MMUT RAC2 F11 KIF1B RAB27A SLC2A10 RREB1 SLC2A1 SLC19A3 CST3 MPL SLC35A1 FANCC CD46 PGM3 F9 SLC4A1 SLFN14 LRP5 NFKBIL1 CYP4F22 G6PC RPS7 F11 MCM4 ABCC2 HLA-DRB1 AMMECR1 SERAC1 ABHD5 TICAM1 SARS2 SBDS TERT GP1BB EFL1 COX4I2 STING1 KRAS CA2 FARS2 ABCC6 DKC1 CYBC1 USP18 MAX WAS SP110 PALB2 UBR1 PUS1 C1R PRTN3 MSH2 RECQL4 SALL4 IL2RB MEFV RAC2 PIGL MPL ATP7B RPL27 USP8 LCAT CCND1 C3 XYLT1 TERT ENG CD59 CD109 CEL TBXA2R DPAGT1 SRP72 MPO TRNF LPIN2 CD247 VKORC1 COL3A1 DNAJC19 PTEN SMPD1 AK2 FLI1 STK11 BEST1 RPL11 CALR ITCH CRYAB PTPN22 COPA TUBB1 CFHR1 PRKAR1A CTCF RPS29 ATRX SCO2 DGKE MYSM1 USP8 SLC29A3 KIF1B CD3E ZMPSTE24 MTR PML ARFGEF2 TRNT1 VHL SRP54 SRP54 SMAD3 SLC27A4 AKR1D1 SMARCAL1 SC5D ATP7A SPTA1 SLC39A13 TYROBP ABCC6 COL3A1 TDP2 C1GALT1C1 GSN FANCL SDHB PEX14 ATRX HSPA9 ABCC8 BCL2 TERC SF3B1 TTN CYSLTR2 SMARCB1 F7 SERPINE1 USB1 SLC22A4 HBB GATA1 PSMB9 RFXAP COL4A1 ACD CP TMEM127 GYPC ABCB7 IGH CD28 FANCI FAM111A LMBRD1 HBG2 FYB1 TMEM127 RHAG ALDOB TNFRSF13C TBC1D24 CD27 UBAC2 ACAD8 RFT1 NLRP3 PNP USB1 TSC2 PTPN11 GNA11 ADA HSD3B7 RAG2 RMRP PRSS1 FDX2 VKORC1 CLCN7 NGLY1 TF NCF1 JAK2 SCN9A SEC61A1 F2 ERMARD TGFB2 STEAP3 LMBRD1 RB1 MYH11 TARS1 CLDN1 RET FGA TNFSF11 BRIP1 PNPO APP ITGB2 COL1A1 P2RY12 AMMECR1 RPS10 KRAS SDHAF2 TRAF3 PDGFRB HBB GATA2 ITGB4 SAMD9L TNNI3 GNAS MYBPC3 IGH SDHA TPM1 FANCD2 SDHA XIAP TCIRG1 NHLRC2 LIG4 PRKAR1A COL7A1 BRCA2 KCNJ1 DLL4 RMRP SDHC HBA2 NUP214 EPB42 C1S TRNW THPO RPL11 IL2RA KIT PRKAR1A BCS1L MYPN SAMD9 PACS2 TRNH KRT14 PLAT TCF3 RPS19 GPR35 HPS4 TBX1 PRKCD KCNJ5 SGCD ACTA2 SCARB2 NLRP3 APOE TCIRG1 RAG2 FLI1 DNMT3A FAN1 PKLR FAS FERMT1 CYP7B1 PROC HADH ADAM17 VPS13B PRKACG LPP BLOC1S3 TBK1 ATP6V0A2 COLGALT1 CTC1 TAL1 RNF168 LIPT1 IFNGR1 BCL10 COL1A1 XRCC4 GALT PLA2G4A KLF11 SF3B1 WDR19 GNAQ IGLL1 SURF1 TALDO1 FGG AGXT PDCD10 MPL MMADHC HK1 GP1BA ENG PRSS1 PDGFRA PDE11A CTPS1 BAP1 ATP7A TLR3 PEX13 AMMECR1 GGCX FGA XK APPL1 CPT2 PEX6 XPR1 TNFRSF1B YARS2 DCLRE1C EVC2 HABP2 COL5A1 AHCY XRCC4 MYH7 APP IL12A WT1 FASLG IKZF1 STOX1 RPS29 BUB1 PRKACA KRT5 ENG SDHD FGFR2 PSMB8 STS IL12A-AS1 WFS1 MLH1 SMAD4 TINF2 COX10 DOLK ASXL1 PEX2 LYRM7 ATP6V0A2 DHFR RPL15 HBA1 LCK RANBP2 TGFBR2 NDE1 DNMT3A RFT1 LZTR1 NEDD4L WAS STN1 PTEN SEMA4A EPB42 NBN UFD1 MYSM1 APP SMAD4 RNASEH2A LRBA C4A ARHGEF1 DNAJC21 ITGA2B HMGCL RAG1 HELLPAR TNNT2 NFKB2 FBN1 NOP10 JMJD1C RAF1 FGB CD46 HMCN1 PALB2 RAG2 FAT4 DGUOK FCGR2A ITGA2B HPRT1 POT1 TBCE POMP ABL1 FUT8 DES FAS NCF1 PROC RAD51 EWSR1 MMAA INHBA CAT FGA PIGL PEX19 SEMA3E FGB EPB41 IFNG LBR EVC LAMTOR2 VWF LRP5 CCND1 MET RPL5 ITGB3 CST3 CYB5A HBA2 LEP LAMA3 KRT5 IRF2BP2 TCF4 TCIRG1 STAT4 CTNNB1 KRT1 CORO1A STK11 SPATA5 NRAS FGG SF3B1 ACP5 CD19 RPL26 CSF3R DLD AK1 DTNBP1 ADAMTS2 NEBL NLRP12 RPS24 RNF113A HMGCL JAK2 BLM LBR HBB TNFRSF1A EPAS1 KIF15 PCCA SH2B3 ABCD3 BRAF TINF2 AGGF1 RAG1 UROS F8 IREB2 SALL4 CPA1 KIT ALPL BMPR1A DNAJC21 CYBB FANCB LAMA3 RPS28 PLN PDGFB CYP11B1 CACNA1D MSH6 RUNX1 DOLK CD247 HBG2 PADI4 WRAP53 PANK2 ATP6AP1 SMAD3 ERCC3 HRG CTLA4 ETV6 CFTR STK4 F2 ND6 PET100 EP300 CHIC2 NLRC4 XYLT2 HBG1 COX15 DSG2 SCN10A DOCK8 DNAJC19 PRF1 SC5D PIGM PMM2 SPINK1 LIPA HAVCR2 IL10 KLRC4 NOS3 SAMD9L ALAS2 KIF1B SLC30A10 F9 MTOR HBB ENPP1 POLG LAMC2 NLRP3 HPS5 FH LAMB3 SLC37A4 MCFD2 HBD KLHDC8B CEBPE HBA1 JAK2 SHPK ISCU DNM1L ELANE IDH2 MAGT1 GNA14 CAD IL7R ACAD9 ESCO2 HPS6 LRP5 NSMCE2 COL14A1 RHBDF2 MPL MMACHC IFIH1 JAK2 SLC40A1 NCF2 RPL18 LIG4 SURF1 FANCG ITGB3 SLC35C1 MYC CD79A SBDS BRIP1 BCR KRIT1 PDGFRA BLNK ANKRD1 ALG8 CD4 MSH6 APP TALDO1 BUB1B CTLA4 CD81 GCK RAD54L NOTCH1 STIM1 DBH NCF4 SMAD4 STAT1 TTC37 TMEM165 RPS14 BCR CD244 PRF1 MSN C4A TNFRSF13B CALR PTPN22 SPINK1 CD28 ATP7A CIITA F13A1 ABHD5 LARS1 TET2 GFI1 CFHR3 PROS1 MFAP5 PKLR BMS1 SLC25A15 TNFRSF13C SLC4A1 F10 MGAT2 SKIV2L CXCR4 CLN3 RTEL1 SLC46A1 CD55 TLR4 GFI1 TINF2 NPC2 RBM8A PLEC NDUFAF5 COG4 SDHB AP3D1 ELMO2 IL10 ITGB3 DDX41 SAR1B RAG1 RBM20 LMAN1 COA8 TFRC CASP10 EXTL3 STAT4 PLEC ARVCF SH2D1A ERF COX3 ZAP70 C15ORF41 RNU4ATAC RNASEH2C TYMP COL5A1 GPX1 TREX1 NDUFA4 FH GCLC COG6 COG4 SLC7A7 CYBA NLRP1 CBL RFX5 MS4A1 CFHR1 JAGN1 PLAU PUF60 COL1A2 AIRE BPGM TRNS2 BLOC1S6 FANCG SAMHD1 LIG4 TNFRSF4 CFHR3 NLRP3 IRAK4 PRKG1 PRSS2 DIAPH1 SLC4A1 HBA2 BLK SNX10 KIT RRM2B AAGAB ITGA2B RARA CD40 NEUROD1 PHF21A MLH1 FANCB FKBP14 EXTL3 GP1BB XIAP CTNNB1 SPTB PIK3R1 NAGS DMD TTC7A JAK2 APC PMS2 PRSS2 PLEC PLOD1 GP1BA MRAS FAS STXBP2 HBB NBN PTPRC KRT14 VPS33A GP1BA MAD2L2 FECH AP3B1 CDKN2A TBXAS1 ERBB3 A2ML1 WIPF1
Protein Mutations 3
C282Y H63D T315I
HP:0000819: Diabetes mellitus
Genes 530
IL2RA HGSNAT ABCC8 RP1 APPL1 ND5 TCF4 GPR101 TRNS2 INSR IER3IP1 TWNK RRM2B HYMAI MAK BSCL2 IFT172 SPINK1 BEST1 XRCC4 HNF1B FSCN2 CTRC PWRN1 TRNL1 KCNJ11 ATM STOX1 ABCC8 ENPP1 CRX COX3 BBS2 CRB1 IGF1R PRKACA TINF2 FOXP3 KCNJ11 TRNS1 IRS2 MAFA HNF1B RP9 PDE4D MST1 TRNL1 WFS1 LMNB2 KLF11 GLIS3 SUFU PDE4D ATP6 DNAJC21 PRPF4 KCTD1 ND1 TUB CYTB RHO INS HBB NDUFS1 CLCNKB ZFYVE26 HFE COX2 CTRC INS GCK EIF2AK3 SAG KRAS GLI2 PALB2 CORIN USH2A NHP2 BSCL2 PRPF6 FGF8 PDX1 LIPE RNASEH2A CNGA1 TDGF1 MERTK AEBP1 PDE11A CP PPP1R3A FOS ARHGEF18 PLCD1 SLC29A3 IDH3B LMNA ND1 TRNQ PRPF3 SLC7A14 NDP XRCC4 PAX4 PDX1 MAPK8IP1 ND3 SNORD116-1 SLC2A2 IPW PTF1A INS CEL PAX4 PTF1A LIG4 HMGA2 HMGA1 NDUFS2 TRNS1 RETN POLD1 PPARG ALMS1 PROK2 FGFR1 PCNT INS LRP6 CAT HNF1A CTNNB1 COX2 INSR POLG2 SCAPER PRCD PCARE HYMAI CFTR DHDDS ZIC2 SLC25A4 LEPR BLM GJA1 KCNJ11 ZNF513 FBN1 AKT2 MMP2 LEP ARMC5 CAV1 PTPN22 GUCA1B GCK GCK PDE8B LMNA NEUROG3 FXN GATA6 SLC16A2 SNORD115-1 PAX4 BMP2 TRNL1 AMACR PTPN1 RAC1 PPARG GJA1 FLT1 PNPLA2 ZFP57 BRCA2 STAT1 SLC30A8 SBDS PDX1 POC1A ROM1 C8ORF37 PDE6B DISP1 CTNS PDE6G COX1 ZMPSTE24 IRS1 GCK LIPE ELN ABCC8 FXN DKC1 RGR HNF1A ND5 SIX3 ND4 TREX1 PROM1 SEMA4A CNBP ARL6 MEN1 TRNQ CPA1 HNF1A CAV1 ABCA4 MAGEL2 ELN TULP1 COX1 REEP6 ABCC8 NDUFA11 PLIN1 NDUFAF2 GCK DHX38 WRN HLA-DRB1 GJB4 NDUFB9 FOXP3 LEMD3 PPARG FOXRED1 DLL1 NDUFS7 MMP14 RP2 WRN RLBP1 SARS2 WRAP53 EFL1 RFC2 SLC19A2 NDUFAF1 TERC CFTR ND6 CDKN2A LMNA SPINK1 STAT3 UBR1 CIDEC ND6 DNAJC3 PLIN1 WFS1 ZFP57 ATM STUB1 HNF1B ARL3 IFT88 BRCA1 CEL TRNC OFD1 TERT DCAF17 TRNF NODAL MKRN3-AS1 NDUFA6 PNPLA2 SPINK1 NDUFAF4 PIK3R1 RDH12 STAT3 ND2 ITCH HNF1A FOXC2 APPL1 IDH3A CASR CNOT1 EDA2R PLAGL1 CYP19A1 POMGNT1 INSR AGPAT2 SLC12A3 WFS1 CISD2 GLRX5 HNF4A IL6 LIMK1 LHX1 TBL2 INS BLK PNPLA6 USP8 SLC29A3 RNASEH2B ZMPSTE24 ARL2BP IMPG2 TWNK TRNF TGIF1 GATA3 ZBTB20 RBP3 KIZ SRP54 PRPF8 TOPORS PEX10 DNM1L GJB3 NDUFS4 DNAJC3 ITPR3 RPGR FUZ NDUFS3 SOX2 GATA6 HERC2 PEX1 TRNW PDX1 TKT FAM161A AR LEPR HNF1A NSMCE2 WFS1 IFIH1 ELMO2 ARNT2 TP53 CEP19 NDUFS6 BBS1 FGFR1 HYMAI NDUFAF3 CLIP2 NDUFV1 SLC19A2 INSR NR2E3 MKKS KIAA1549 TMEM126B CP PPP1R15B KLHL7 CNGB1 GCK GCGR PTRH2 MC4R ADAR APOA5 GAS1 TIMMDC1 STAT1 AGBL5 PARN EIF2AK3 SHH FOXH1 NDUFAF5 PROKR2 WFS1 CA4 KDSR SPINK1 HNF1A TRNK KCNJ11 USB1 PAX4 EYS NEK2 PRSS1 CERKL NDUFS8 ND1 LMNA TRNK MKRN3 ERGIC1 BRAF HNF1B MOG RTEL1 POLG CCDC28B CDH23 PEX6 TRNV NDN LMNA NDUFB10 PIK3R1 KCNJ11 ZNF408 HESX1 KCNJ11 UBR1 GNAS PRSS1 ALMS1 HBB BBS2 GCK CDHR1 PRPF31 SMAD4 AIP NEUROD1 HAMP NDUFB11 TTPA TRNE AKT2 ABCC8 DMXL2 GTF2I CTRC TRNW COX3 POLR3A MTNR1B IL2RA LRAT PRKAR1A KCNJ11 HNF4A PRPH2 RNASEH2C LMNA CLRN1 TRNH OPA1 NPM1 ABCC8 HFE NRL PDE6A APOE GPR35 HNF4A AIRE TRNS2 MLXIPL GPD2 LMNA TTC8 SAMHD1 EDA TP53 NUBPL SNRPN TRMT10A NKX2-5 PWAR1 RPE65 PDX1 IGF2BP2 PRSS2 PRKACA AHI1 CAVIN1 PTCH1 BLK PPARG SPATA7 NPAP1 EIF2S3 BAZ1B SNRNP200 HNF4A POLA1 AHR NEUROD1 NDUFV2 PDX1 PSTPIP1 HJV AIP PALLD HLA-DQB1 TRNE TCF7L2 CTC1 NSMCE2 TTC7A NOP10 OTX2 PRSS2 PRKAR1A XRCC4 SOX3 HNF4A IMPDH1 NDUFB3 IFT140 DCAF17 KLF11 NEUROD1 FOXP1 CDON LIPC PLAGL1 CISD2 NDUFA1 PRSS1 GTF2IRD1 VANGL1 AGPAT2