There are 3 clinical trials

Clinical Trials

1 The Role of the Functionally Relevant Single Nucleotide Polymorphisms CYP2J2 -50G>T (CYP2J2 7) and EPHX2 9846A>G (EPHX2 K55R) in Human Endothelial Function

Background: - The endothelium is the inner lining of blood vessels. The cells in this lining help regulate blood flow and immune system function. Problems with endothelial cells can contribute to heart disease, high blood pressure, and diabetes. Certain genes or parts of genes may be related to problems with endothelial function. Researchers want to study healthy adults who have genes that may affect their endothelial function. More information on these genes may provide more information on genetic risk for certain diseases. Objectives: - To study healthy adults who have genetic markers related to endothelial cell problems. Eligibility: - Healthy volunteers between 18 and 65 years of age. - Current participants of the Environmental Polymorphisms Registry and have certain genes related to endothelial cell problems. Design: - Participants will have a single study visit to collect information and samples. - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. - Participants will have an ultrasound of the artery in the arm and will be given a short-acting medication called nitroglycerin to study blood flow and blood pressure.

NCT01524549 Cardiovascular Disease

MeSH:Cardiovascular Diseases

HPO:Abnormality of the cardiovascular system

The Role of the Functionally Relevant Single Nucleotide Polymorphisms CYP2J2 -50G>T (CYP2J2 7) and EPHX2 9846A>G (EPHX2 K55R) in Human Endothelial Function. --- K55R ---

- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R ---

- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R ---

- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R --- --- K55R ---

- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R --- --- K55R --- --- K55R ---

- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R --- --- K55R --- --- K55R --- --- K55R ---

This is a cross-sectional, controlled study designed to investigate the association of two single nucleotide polymorphisms (SNPs) - a cytochrome P450 (CYP) epoxygenase gene CYP2J2 SNP, CYP2J2 7, and a soluble epoxide hydrolase (sEH) gene EPHX2 SNP encoding a K55R variant - with altered endothelial function in humans. --- K55R ---

Healthy adults, aged 18-65 years, who are either carriers of CYP2J2 7 or EPHX2 K55R, or who are wild type (WT) with respect to either SNP will be recruited into a total of five genotype groups. --- K55R ---

The primary objective of the study is to determine whether individuals who are homozygous or heterozygous for the CYP2J2 7 or EPHX2 K55R SNPs exhibit altered endothelial function compared with individuals who are WT for that SNP. --- K55R ---

2 Role of Epoxyeicosatrienoic Acids in Chronic Allograft Nephropathy

Endothelial lesions within the transplanted kidney are a major determinant of chronic allograft nephropathy. Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors with anti-inflammatory, antiproliferative and vasodilator properties. The main goal of the investigators' study is to evaluate whether genetic polymorphisms of specific enzymes responsible for the bioavailability of EETs are associated with post-transplant kidney function. To this end, 80 kidney transplant recipients will be included. Prespecified genetic polymorphisms of CYP 2J2, CYP 2C8, CYP 2C9, CYP 2C9, CYP 2C19 and EPHX2 will be determined. Kidney function will be recorded 3, 6, 12 and 36 months after transplantation. Flow-mediated dilatation, EETs and circulating biomarkers of endothelial function will be measured in the radial artery. The expected results of this study to provide preliminary evidence supporting a beneficial role of an increase in the bioavailability of EETs in kidney transplant recipients.

NCT02555566 Kidney Transplant Recipients Procedure: Blood sampling Procedure: flow-mediated distal stimulation of the forearm radial artery by cutaneous heating

MeSH:Kidney Diseases

HPO:Abnormality of the kidney Nephropathy

Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR). --- Lys55Arg ---

3 Cytochrome P450 Epoxygenase Pathway Regulation of Macrophage Function

Background: Respiratory diseases affect more than 1 billion people worldwide. They are a growing public health concern. The lungs are constantly exposed to environmental factors such as dust, fumes, microbes, and pollutants. But much is still not known about how these pollutants lead to respiratory illnesses. Researchers want to collect samples from lungs and blood to see how genetics and environmental pollutants affect cellular responses or functioning. Objectives: To study how cytochrome P450 epoxygenase pathway enzymes affect macrophage function in the lungs and inflammatory responses. Eligibility: Adults ages 18 65 who can have a bronchoscopy. Design: All study visits will take place at the NIEHS Clinical Research Unit in Research Triangle Park, NC. At study visit 1, participants will be screened with medical history and physical exam. They will have blood and urine tests. They will take tests that measure their lung function. They will answer questionnaires. Before the visit, they will be given a list of medicines they cannot take. They also must not have caffeine on the day of their visit. The visit will last about 3 hours. At study visit 2, participants will give blood samples. They will undergo bronchoscopy. For this, they will get an intravenous line in a vein to get sedatives. Their airways will be numbed. Cells will be collected from their lungs. They will fast for 8 hours before the visit. They must have someone else drive them home from the visit. The visit will last about 3-4 hours. Participants will get a follow-up phone call about 1 day after study visit 2.

NCT02743468 Polymorphism Lung Inflammation

MeSH:Pneumonia Inflammation

HPO:Pneumonia

- INCLUSION CRITERIA: 1. Age 18 to 65 years, inclusive (males and females) 2. Able to travel to the NIEHS CRU for required study visits 3. Able to present a valid government-issued form of identification for entry to the NIEHS campus 4. Able to fast for 8 hours prior to the visit where bronchoscopy occurs 5. Has a responsible party who is willing and able to attend Visit 2 and drive the participant away from the CRU after completion of Visit 2, if the participant elects to undergo conscious sedation 6. Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - Wild type with respect to EPHX2 K55R, EPHX2 R287Q, and CYP2J2*7; or - Homozygous for EPHX2 K55R (wild type for the other SNPs); or - Homozygous for EPHX2 R287Q (wild type for the other SNPs); or - Homozygous for CYP2J2*7 (wild type for the other SNPs) EXCLUSION CRITERIA: 1. --- K55R ---

- INCLUSION CRITERIA: 1. Age 18 to 65 years, inclusive (males and females) 2. Able to travel to the NIEHS CRU for required study visits 3. Able to present a valid government-issued form of identification for entry to the NIEHS campus 4. Able to fast for 8 hours prior to the visit where bronchoscopy occurs 5. Has a responsible party who is willing and able to attend Visit 2 and drive the participant away from the CRU after completion of Visit 2, if the participant elects to undergo conscious sedation 6. Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - Wild type with respect to EPHX2 K55R, EPHX2 R287Q, and CYP2J2*7; or - Homozygous for EPHX2 K55R (wild type for the other SNPs); or - Homozygous for EPHX2 R287Q (wild type for the other SNPs); or - Homozygous for CYP2J2*7 (wild type for the other SNPs) EXCLUSION CRITERIA: 1. --- K55R --- --- R287Q --- --- K55R ---

EXCL 4. Any food or fluids for 8 hours prior to the bronchoscopy - INCLUSION CRITERIA: 1. Age 18 to 65 years, inclusive (males and females) 2. Able to travel to the NIEHS CRU for required study visits 3. Able to present a valid government-issued form of identification for entry to the NIEHS campus 4. Able to fast for 8 hours prior to the visit where bronchoscopy occurs 5. Has a responsible party who is willing and able to attend Visit 2 and drive the participant away from the CRU after completion of Visit 2, if the participant elects to undergo conscious sedation 6. Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - Wild type with respect to EPHX2 K55R, EPHX2 R287Q, and CYP2J2*7; or - Homozygous for EPHX2 K55R (wild type for the other SNPs); or - Homozygous for EPHX2 R287Q (wild type for the other SNPs); or - Homozygous for CYP2J2*7 (wild type for the other SNPs) EXCLUSION CRITERIA: 1. --- K55R ---

EXCL 4. Any food or fluids for 8 hours prior to the bronchoscopy - INCLUSION CRITERIA: 1. Age 18 to 65 years, inclusive (males and females) 2. Able to travel to the NIEHS CRU for required study visits 3. Able to present a valid government-issued form of identification for entry to the NIEHS campus 4. Able to fast for 8 hours prior to the visit where bronchoscopy occurs 5. Has a responsible party who is willing and able to attend Visit 2 and drive the participant away from the CRU after completion of Visit 2, if the participant elects to undergo conscious sedation 6. Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - Wild type with respect to EPHX2 K55R, EPHX2 R287Q, and CYP2J2*7; or - Homozygous for EPHX2 K55R (wild type for the other SNPs); or - Homozygous for EPHX2 R287Q (wild type for the other SNPs); or - Homozygous for CYP2J2*7 (wild type for the other SNPs) EXCLUSION CRITERIA: 1. --- K55R --- --- R287Q --- --- K55R ---

HPO Nodes