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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation A1166C

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 4 clinical trials

Clinical Trials


1 Optimal Dose of Irbesartan for Renoprotection in Type 2 Diabetic Patients With Persistent Microalbuminuria

Aim: To evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultra high doses of irbesartan in Type 2 diabetic patients with microalbuminuria Design: A double-masked randomized cross-over trial including 60 hypertensive Type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication. At inclusion, previous antihypertensive treatment will be discontinued and replaced with bendroflumethiazide 5 mg o.d. for the entire study. Following two months wash-out (baseline), patients will be treated randomly with irbesartan 300, 600 and 900 mg o.d., each dose for two months. End-points evaluated at the end of each study period include urinary albumin excretion rate (UAE, mean of three 24-hrs collections), 24-hrs blood pressure (ABP); and GFR (51Cr-EDTA).

NCT00320879
Conditions
  1. Type 2 Diabetes
  2. Microalbuminuria
Interventions
  1. Drug: irbesartan
MeSH:Albuminuria
HPO:Albuminuria

Initially we will evaluate the influence of the ACE/ID- , Angiotensin II type I receptor (A1166C) - and the angiotensinogen (M235T) polymorphisms. --- A1166C ---

Primary Outcomes

Measure: urinary albumin excretion rate

Secondary Outcomes

Measure: ambulatory blood pressure

Measure: glomerular filtration rate

Measure: serum potassium

Measure: serum creatinine

Measure: lipids

Measure: renin

Measure: aldosterone

Measure: NT-proBNP

Measure: markers of endothelial function

Measure: markers of inflammation

Measure: genotypes with possible implications for the risk of cardiovascular disease

2 A Randomized, Open Label, Cross-over Comparative Study of Irbesartan/Hydrochlorothiazide and Irbesartan in the Treatment of Mild to Moderate Hypertension

Primary: 1. To compare the change in forearm vascular resistance following a 12-week regimen of irbesartan/hydrochlorothiazide versus irbesartan 2. To assess changes of serum proinflammatory cytokine, markers of cardiovascular risks, oxidative stress and circulating adhesion molecule including thiobarbiturate acid reactive substances (TBARS), C-reactive protein (CRP), interleukin 6 (IL-6), and vascular cell adhesion molecule 1 (VCAM-1). Secondary: 1. To compare the reduction in office blood pressure following a 12-week regimen of irbesartan/hydrochlorothiazide versus irbesartan 2. To compare the response rate (defined as office Systolic blood pressure(SBP)/diastolic blood pressure (DBP) reduce more than 10mmHg from baseline), and BP controlled rate (defined as SBP<140 mmHg and /or DBP<90 mmHg) 3. To ascertain the safety and tolerability of irbesartan / hydrochlorothiazide versus irbesartan when administered once daily 4. To determine whether angiotensin II type 1 (AT-1) receptor gene polymorphisms (including A1166C gene with about 4% of the minor allele frequency in Chinese population and other single nucleotide polymorphisms with a higher frequency of about 10% of minor allele) is related to reduction of BP

NCT00443612
Conditions
  1. Hypertension
Interventions
  1. Drug: Irbesartan/Hydrochlorothiazide
  2. Drug: Irbesartan
MeSH:Hypertension
HPO:Hypertension

To compare the reduction in office blood pressure following a 12-week regimen of irbesartan/hydrochlorothiazide versus irbesartan 2. To compare the response rate (defined as office Systolic blood pressure(SBP)/diastolic blood pressure (DBP) reduce more than 10mmHg from baseline), and BP controlled rate (defined as SBP<140 mmHg and /or DBP<90 mmHg) 3. To ascertain the safety and tolerability of irbesartan / hydrochlorothiazide versus irbesartan when administered once daily 4. To determine whether angiotensin II type 1 (AT-1) receptor gene polymorphisms (including A1166C gene with about 4% of the minor allele frequency in Chinese population and other single nucleotide polymorphisms with a higher frequency of about 10% of minor allele) is related to reduction of BP Forearm vascular resistance. --- A1166C ---

Primary Outcomes

Measure: Forearm vascular resistance

Time: At baseline and end of study

Measure: Changes of serum TBARS, CRP, IL-6, and VCAM-1

Time: Throughout the study period

Measure: Office BP measurement of seated SBP and DBP

Time: At baseline and after 12-week treatment

Measure: Adverse events

Time: Throughout the study period

Secondary Outcomes

Measure: Office BP measurement of seated SBP and DBP

Time: At baseline and after 12-week treatment

3 Observational Study of the Polymorphisms of the Renin-angiotensin-aldosterone System and Their Relation to Resistant Systemic Arterial Hypertension and Adverse Cardiovascular Events

Renin-angiotensin-aldosterone system (RAAS) polymorphisms influence 24h arterial pressure fluctuation. Resistant systemic arterial hypertension (RSAH) has an increased risk of end organ damage and unfavourable prognosis, whereas pseudo-RSAH usually respond favourably to drug therapy. To prospectively investigate, in subjects with RSAH in a tropical South American city: 1) Adverse cardiovascular events defined as fatal and non-fatal stroke or acute myocardial infarction (AMI); and 2) the association of RAAS polymorphisms and adverse cardiovascular events in this population. Study population: 212 hypertensives recruited from primary care assistance (time since first diagnosis of hypertension: 16.5±8.1 years) and without appropriate pressure control, between 2001 and 2006, corresponding to 0.48% of all hypertensives under care (18 new cases/year), 57±10 years old, 66% females. Under drug treatment schedule: three or more drugs including a diuretic. Ninety two randomly selected hypertensives basis had renin-angiotensin-aldosterone system genetic profile determined. Genetic assessment was carried out using a polymerase chain reaction assay amplification technique. The following single nucleotide polymorphisms were analyzed: renin (G1051A), angiotensinogen (M235T), angiotensin converting enzyme-ACE (I/D), angiotensin II type 1 receptor (A1166C), aldosterone synthase (C344T) and mineralocorticoid receptor (G3514C).

NCT01173029
Conditions
  1. Systemic Arterial Hypertension
  2. Hypertension Resistant to Conventional Therapy
  3. Myocardial Infarction
  4. Stroke
Interventions
  1. Drug: Anti-hypertensive drug treatment
MeSH:Hypertension Myocardial Infarction Coronary Vasospasm Infarction
HPO:Hypertension Myocardial infarction

The following single nucleotide polymorphisms were analyzed: renin (G1051A), angiotensinogen (M235T), angiotensin converting enzyme-ACE (I/D), angiotensin II type 1 receptor (A1166C), aldosterone synthase (C344T) and mineralocorticoid receptor (G3514C). --- G1051A --- --- M235T --- --- A1166C ---

Primary Outcomes

Description: Evidence of clinically definite stroke (focal neurological deficits persisting for more than 24 hours) confirmed or not by non-investigational computerized tomography. Death was considered to be related to the event if occurring up to 30 days after the acute event. Assessment twice an year by active and direct contact to patients or relatives and review of medical records.

Measure: Strokes, Either Fatal or Nonfatal

Time: up to 10 years

Secondary Outcomes

Description: Evidence of clinically definite stroke (focal neurological deficits persisting for more than 24 hours) confirmed or not by non-investigational computerized tomography. Evidence of clinically definite acute myocardial infarction (prolonged > 20min chest pain, not relieved by sublingual nitrate, ST-T segment deviation on 12-lead surface ECG, elevation of plasma troponin >0.2 ng/dL 6h following chest pain episode). Death was considered to be related to the event if occurring up to 30 days after the acute event. Assessment twice an year by active and direct contact to patients or relatives and review of medical records.

Measure: Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal

Time: up to 10 years

4 Investigating the Involvement of ACE and Angiotensinogen Genes' Polymorphism Along With Other Thrombophilic Genotypes in Severe Forms of COVID-19 With/Without Thrombotic Events

An estimated 22% of the global population is at an increased risk of a severe form of COVID-19, while one in four coronavirus patients admitted to intensive care unit will develop a pulmonary embolism. A major public health question remains to be investigated: why COVID-19 is mild for some, critically severe for others and why only a percentage of COVID-19 patients develop thrombosis, despite the disease's proven hypercoagulable state? Patients' intrinsic characteristics might be responsible for the deep variety of disease forms. Our study aims to assess the validity of the hypothesis according to which underlining genetic variations might be responsible for different degrees of severity and thrombotic events risks in the novel coronavirus disease. Moreover, we suspect that prothrombotic genotypes occuring in the genes that encode angiotensin-converting enzyme (ACE-DEL/INS) and angiotensinogen (AGT M235T) are involved in the unpredictable evolution of COVID-19, both in terms of severity and thrombotic events, due to the strong interactions of SARS-CoV-2 with the renin-angiotensin-aldosterone system (RAAS). Therefore, we also aim to assess the validity of the theory according to which there is a pre-existing atypical modulation of RAAS in COVID-19 patients that develop severe forms and/or thrombosis. Our hypothesis is based on various observations. Firstly, there is a substantial similarity with a reasonably related condition such as sepsis, for which there is a validated theory stating that thrombophilic mutations affect patients' clinical response. Secondly, racial and ethnic genetic differences are responsible for significant dissimilar thrombotic risks among various nations. Thirdly, an increase in stroke incidence has been reported in young patients with COVID-19, without essential thrombosis risk factors, favoring the idea that a genetic predisposition could contribute to increase the thrombotic and thromboembolic risk. Fourthly, the plasminogen activator inhibitor (PAI)-1 4G/5G inherited mutation was found to be responsible for a thrombotic state causing post-SARS osteonecrosis.

NCT04519398
Conditions
  1. Covid19
  2. Corona Virus Infection
  3. Thrombosis
  4. ARDS
  5. Thrombophilia
  6. Thromboses, Intracranial
  7. Thromboses, Deep Vein
  8. RAAS
Interventions
  1. Genetic: Complete thrombophilic profile testing by multiplex PCR
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Intracranial Thrombosis Thrombosis Venous Thrombosis Thrombophilia
HPO:Deep venous thrombosis Hypercoagulability Venous thrombosis

Inclusion Criteria: - All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test Exclusion Criteria: - Patient refusal - Uncertain tests results - Children Inclusion Criteria: - All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test Exclusion Criteria: - Patient refusal - Uncertain tests results - Children Covid19 Corona Virus Infection Thrombosis ARDS Thrombophilia Thromboses, Intracranial Thromboses, Deep Vein RAAS Coronavirus Infections Severe Acute Respiratory Syndrome Intracranial Thrombosis Thrombosis Venous Thrombosis Thrombophilia The study's protocol will cover the following steps: • Collected data from COVID-19 patients at admission will include: - Descriptive general demographic data - Previous pathologies and thrombosis risk factors - Routine biological data (the blood routinely collected will also be used for SARS-Cov-2 specific RT-PCR exam) Complete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes: - Factor V Leiden - Factor V 4070 A G (Hr2) - Factor II G20210A - Methylenetetrahydrofolate reductase (MTHFR) C677T - MTHFR A1298C - Cystathionine β-synthase (CBS) 844ins68 - PAI-1 4G/5G - Glycoprotein IIIa T1565C (HPA-1a/b) - ACE-DEL/INS - Apolipoprotein E (ApoE) - AGT M235T - Angiotensin II type 1 receptor (ATR-1) A1166C - Fibrinogen - 455 G A - Factor XIII Val34Leu SpO2, respiratory rate, PaO2/FiO2 RAAS components - Imagistic procedures (chest X-ray or CT) - All patients with a positive SARS-CoV-2 PCR test will be included - Patients will be divided into three groups depending on disease severity and the presence of thrombotic state: - 1st group includes COVID-19 patients with proved - venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms) - or arterial thrombosis (heart attacks, strokes) - 2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 ≥ 94% - 3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency > 30 breaths per minute, SpO2 < 94%, PaO2/FiO2 < 300 mmHg, or lung infiltrates >50% - Statistical methods will be employed to check for significant differences between prothrombotic mutations frequency and RAAS components levels for the three groups --- G20210A --- --- C677T --- --- A1298C --- --- T1565C --- --- M235T --- --- A1166C ---

Primary Outcomes

Description: The difference of prothrombotic genotypes frequency between the three groups

Measure: Number of patients with thrombophilic profile alterations

Time: One year

Secondary Outcomes

Description: The differences of RAAS components levels between the three groups

Measure: Number of patients with RAAS components alterations

Time: One year


HPO Nodes


HP:0000822: Hypertension
Genes 421
ELN FBN1 SDCCAG8 PRKAR1A ALX4 LIMK1 PDE11A NR3C2 FBN1 KCTD1 VHL GP1BB ANGPTL6 ENPP1 MLXIPL NKX2-5 LEMD3 NOTCH2 SLC37A4 RET SEC24C BBS12 NPHP1 MMP14 EGFR HLA-DPB1 KCTD1 ABCG8 SCNN1A SLC25A11 COX3 CYTB TRAF3IP1 HGD MEF2A VHL PKD1 TRIP13 GANAB RPGRIP1L ITGA8 CDH23 BBS7 ELN DIS3L2 SMARCAL1 GATA5 PKD2 NPHP3 KIF1B JMJD1C UFD1 ARMC5 CCR6 SERPINA6 KLHL3 LMX1B BRCA2 GTF2I YY1AP1 TNFRSF11B LMNA CTLA4 G6PC NOTCH1 MDM2 WDR19 MAFB TRPC6 RET LMNA ERCC4 XYLT2 SDHB CACNA1D TMEM67 LZTFL1 ERCC4 COQ7 MYLK KIF1B PTPN22 COL4A5 NPHP1 DNMT3A SCNN1A CACNA1D BBS9 CDH23 WT1 FGFR2 TGFB2 GLA BICC1 TTC8 ND1 ADA2 WDPCP ARHGAP31 ARL6 AIP FGFR2 ALMS1 INVS FBN1 VHL WT1 IDUA SMAD4 CFHR3 PDE11A WNK1 NPHP1 WRN SLC2A10 SMAD6 OSGEP ABCC6 LRIG2 SDHB PRKACA FLT1 INVS HBB POU3F4 NOTCH3 LMNA MC4R PRKACA HLA-DRB1 TRNK MYH7 HSD11B2 MYH11 VANGL1 EDA2R PHF21A MDH2 MKS1 BBS2 DNAJB11 TSC1 CFB MTRR GNAS MTTP PRKAR1A LMNA NF1 MUC1 ND6 HPSE2 CYP11B1 CUL3 EDA NPHP4 ALMS1 VAC14 TRNK SMAD4 THBD OFD1 STAT2 BBS5 SDHD PRKAR1A HMBS APOB ECE1 KCNJ5 REST RET MKKS FMO3 PRTN3 ERCC6 PKHD1 CFHR1 LRP6 CYP11B2 BBS10 SDHD FN1 PCSK9 CBS ZMPSTE24 SDCCAG8 ERCC8 CDKN1A IRF5 C3 TRNL1 PKD1 FUZ COX1 HLA-DPA1 MGP PLIN1 LDLRAP1 CLCN2 SH2B3 LYZ LOX MFAP5 GNAS CYP17A1 CYP11B1 B2M TMEM127 KCNJ5 PAM16 NR3C1 ACAT1 TRNK CDKN1B MEN1 SDHAF2 WT1 STAT1 BNC2 TGFB3 HMBS USP8 BBIP1 LMX1B GANAB HLA-B PDE8B IFT27 LMNA RREB1 MMP2 CYP11B1 TRNL1 ARVCF MLX GCH1 ABCC6 CLIP2 C8ORF37 OFD1 TBX1 CEP164 JAK2 NFU1 FH GJA1 SDHC BAZ1B CFH CYP21A2 JAK2 CEP290 CD2AP TRNQ TRIM32 STOX1 RFC2 AIP RET CYP11B1 LDLR SPRY2 TMEM70 NDUFAF6 GUCY1A1 WT1 CDKN2C TRNF POU6F2 ADA2 IFT172 ADAMTSL4 TRIM28 GNAS BMPR2 TMEM127 PKD2 CORIN CAV1 PRKG1 ABCB6 VHL SLC25A11 EXT2 MAT2A NFIX XPNPEP3 KCNJ5 GBA SCNN1B MAX CACNA1H ENG AIP ACTA2 TRNW ARMC5 H19 SDHD TRNS2 TSC2 COL4A4 BRCC3 FGA PDE3A USP8 SCNN1B FIG4 COX2 ELP1 WDR35 INF2 GPC3 SDHC ACTN4 ABCC6 SCN2B SLC2A10 TRNV SDHA COMT CYP17A1 WNK4 TBX1 SMAD4 BSCL2 ENPP1 SCNN1G BBS1 SUGCT GTF2IRD1 GLA CFI ACVRL1 MPL NOS3 BBS1 APRT APOA1 FOXE3 MAX TGFBR2 XYLT1 TP53 CCDC28B NOD2 ADA2 PLIN1 DLST CC2D2A FN1 COL4A3 BANF1 TGFBR3 SCNN1G LARS2 GDNF SLC37A4 PPOX PKHD1 CEP290 ACP5 KRT18 DZIP1L CCND1 ERCC8 GUCY1A1 TRNC CCN2 SMAD3 KRT8 SDHB FBN1 TGFBR1 SDHD POR COL4A3 BBS4 SDHB IL12B MYMK FMR1 ELN NF1 CEP19 CPOX ARL6 NR3C1 TET2 EPAS1 ND5 DYRK1B PDE3A ELP1 TRIM28 YY1AP1 CD46 TMEM237 TBL2 ERCC6 THSD1 CDKN2B HIRA ACTA2 WT1 KIF1B VHL NSMCE2 GPR101 COL3A1 ABCG5 HSD11B2 PPARG PPARG TNFRSF11A COL3A1 LEMD3 TRNS1 IQCB1 TRNE