Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in patients with heart failure.
We analyzed the possible association between aldosterone synthase (CYP11B2) T-344C polymorphism, which is associated with increased aldosterone activity, and the prevalence of atrial fibrillation (AF) in 196 consecutive patients who had symptomatic systolic heart failure (HF; left ventricular ejection fraction <40%) for > or =3 months before recruitment. Genomic DNA was extracted from peripheral blood leukocytes using a standard protocol. Subjects were genotyped for the CYP11B2 polymorphism using the polymerase chain reaction/restriction fragment length polymorphism approach. AF was present in 63 patients (33%) with HF. We found the -344 CC genotype to be a strong independent marker for AF. Almost 1/2 (45%) of patients with this genotype had AF compared with 1/4 (27%) with -344 TT and TC genotypes (p = 0.01). A multivariate stepwise logistic regression model that included age, gender, New York Heart Association class, CYP11B2 -344CC genotype, and echocardiographic measurements of left ventricular ejection fraction, left atrial dimension, left ventricular end-diastolic diameter, and mitral regurgitation severity showed that the CYP11B2 CC genotype (adjusted for age and left atrial size) was an independent predictor of AF (adjusted odds ratio 2.35, 95% confidence interval 1.57 to 3.51, p = 0.03). In conclusion, CYP11B2 T-344C promoter polymorphism predisposes to clinical AF in patients with HF.
Amir
Offer
O
Heart Failure Center, Department of Cardiovascular Medicine, Lady Davis Carmel and Lin Medical Centers, Haifa, Israel.
Amir
Ruthie E
RE
Paz
Hagar
H
Mor
Roi
R
Sagiv
Michael
M
Lewis
Basil S
BS
D000367:Age Factors; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012044:Regression Analysis; D012737:Sex Factors
D004247:DNA; D019405:Cytochrome P-450 CYP11B2