Serotonin Transporter Gene Polymorphism in Women With Suspected Ischemia: A Report From the NHLBI

Association of serotonin transporter gene (5-HTTLPR) polymorphisms with adverse cardiovascular (CV) events in women with suspected ischemia has not yet been reported. We hypothesized an association of 5-HTTLPR polymorphisms with risk of adverse CV events in women with suspected ischemic heart disease (IHD) referred for coronary angiography enrolled in the Women’s Ischemia Syndrome Evaluation (WISE). We studied clinical and angiographic data and DNA from a cohort of 437 Caucasian women enrolled in the WISE genotyped for the long (L) and short (S) variant of the 5-HTTLPR polymorphism. Women were followed yearly for adverse CV events (defined as first occurrence of all-cause death, myocardial infarction, stroke, or heart failure hospitalization) with data collected at WISE 10-year follow-up. Exploratory analyses compared outcomes between genotype groups. A total of 437 women, with baseline, angiographic, and long-term follow-up data, were successfully genotyped. Their mean age was 58 ± 11 years and body mass index 29 ± 6; 54% had hypertension, 18% diabetes, 50% dyslipidemia, 20% depression history, and only 34% had obstructive CAD. At 8.9 years median follow-up, the SS genotype was associated with significantly increased risk of adverse CV event versus LL + LS (1.93, confidence interval [CI]: 1.03-3.61, P = .03). Results were not significant for all-cause death (hazard ratio: 1.63, CI: 0.91-2.93, P = .09). Among a cohort of Caucasian women with suspected IHD enrolled in the WISE, the SS homozygous genotype for the 5-HTTLPR polymorphism was associated with increased risk of adverse CV outcomes