Dataset Information

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

ABSTRACT: The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n?=?126), serum was also collected for determination of circulating aldosterone. The CYP11B2 -344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 -344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60-98.4, p?=?0.0150, empirical p?=?0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p?=?0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r?=?-0.19, p?=?0.037). The CYP11B2 -344CC genotype was also overrepresented among patients with extreme aldosterone elevation (?90th percentile, p?=?0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 -344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans.

SUBMITTER: Bress A

PROVIDER: S-EPMC3728110 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

Bress Adam A Han Jin J Patel Shitalben R SR Desai Ankit A AA Mansour Ibrahim I Groo Vicki V Progar Kristin K Shah Ebony E Stamos Thomas D TD Wing Coady C Garcia Joe G N JG Kittles Rick R Cavallari Larisa H LH

PloS one 20130730 7

The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determine ...[more]

PMID: 23936266

Similar Datasets

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

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

Publications

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

Publications

Association of aldosterone synthase polymorphism (CYP11B2 -344T&gt;C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.