Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.
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.
Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois, USA.
Adam
A
Bress
Jin
J
Han
Shitalben R
SR
Patel
Ankit A
AA
Desai
Ibrahim
I
Mansour
Vicki
V
Groo
Kristin
K
Progar
Ebony
E
Shah
Thomas D
TD
Stamos
Coady
C
Wing
Joe G N
JG
Garcia
Rick
R
Kittles
Larisa H
LH
Cavallari
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000450:Aldosterone / Q000097:blood*; D000483:Alleles; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000235:genetics*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D044465:White People / Q000235:genetics
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2