Dataset Information

Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study.

ABSTRACT: A single-nucleotide polymorphism in the aldosterone synthase gene (CYP11B2) promoter [-344C/T, rs1799998] has been reported to associate with cardiovascular phenotypes.The Dallas Heart Study is a large, multiethnic cohort with a high prevalence of hypertension. We genotyped 3452 Dallas Heart Study participants for -344C/T. Generalized linear models were used to assess whether variation at -344C/T associated with plasma aldosterone concentration (PAC), systolic and diastolic blood pressure (SBP and DBP), plasma glucose (in persons with no diabetes), HOMA IR (Homeostasis Model Assessment as an Index of Insulin Resistance), and left ventricular (LV) mass indexed to height. Systolic blood pressure and DBP were significantly higher in blacks compared with whites (P < 0.001 for SBP and for DBP) and Hispanics (P < 0.001 for SBP and for DBP). Log-transformed body mass index was also significantly higher in blacks compared with whites (P < 0.001), but not Hispanics (P = 0.10). Log-transformed PAC was higher in whites compared with blacks (P < 0.001), but did not differ significantly in whites compared with Hispanics (P = 0.73). In univariate and multivariable analysis, -344C/T was not significantly associated with PAC within any ethnicity. In univariate and multivariable analysis, -344C/T was not associated with SBP or DBP within any ethnicity. After adjustment for multiple testing, univariate and multivariable analyses revealed no association between -344C/T and plasma glucose in patients with no diabetes, HOMA IR, or LV mass indexed to height.We were unable to reproduce previously reported associations between -344C/T and PAC, blood pressure, plasma glucose, or LV mass. Methodological differences might explain the differences between our findings and those previously reported.

SUBMITTER: Byrd JB

PROVIDER: S-EPMC5568080 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study.

Byrd James Brian JB Auchus Richard J RJ White Perrin C PC

Journal of investigative medicine : the official publication of the American Federation for Clinical Research 20151001 7

<h4>Background</h4>A single-nucleotide polymorphism in the aldosterone synthase gene (CYP11B2) promoter [-344C/T, rs1799998] has been reported to associate with cardiovascular phenotypes.<h4>Methods</h4>The Dallas Heart Study is a large, multiethnic cohort with a high prevalence of hypertension. We genotyped 3452 Dallas Heart Study participants for -344C/T. Generalized linear models were used to assess whether variation at -344C/T associated with plasma aldosterone concentration (PAC), systolic ...[more]

PMID: 26200036

Similar Datasets

Project description:BACKGROUND:The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood. OBJECTIVES:The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care. METHODS:The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ?190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus. RESULTS:Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ?5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64). CONCLUSIONS:In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups.

Project description:Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the Pakistani community prompted us to design this study. Aldosterone synthase (CYP11B2) was thoroughly studied in different ethnic groups; however, no such study has been conducted in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. In essential hypertension, the aldosterone synthase gene (CYP11B2) plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the CYP11B2 gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase (CYP11B2) gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between CYP11B2 gene polymorphism and hypertension in Pakistan's Pashtun population. We used the nascent exome sequencing method to identify variants associated with hypertension. The research was divided into two phases. In phase one, DNA samples from 200 adult hypertension patients (of age ≥ 30 years) and 200 controls were pooled (n = 200/pool) and subjected to Exome Sequencing. In the second phase, the WES reported SNPs were genotyped using the Mass ARRAY technique to verify and confirm the association between WES-identified SNPs and hypertension. WES identified a total of eight genetic variants in the CYP11B2 gene. The chi-square test and logistic regression analysis were used to estimate the minor allele frequencies (MAFs) and chosen SNPs relationships with hypertension. The frequency of minor allele T was found to be higher in cases compared to the control (42% vs. 30%: p = 0.001) for rs1799998 of CYP11B2 gene, while no significant results (p > 0.05) were observed for the remaining SNPs; rs4536, rs4537, rs4545, rs4543, rs4539, rs4546 and rs6418 showed no positive association with HTN in the studied population (all p > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan.

Dataset Information

Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study.

Publications

Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets