Abstract 20055: Serotonin Transporter Gene Polymorphism in Women with Suspected Ischemia: A Report from the NHLBI-sponsored WISE
Introduction: Cardiovascular (CV) risk assessment in women is limited as standard risk stratification schemes underestimate adverse events. Serotonin transporter gene (5-HTTLPR) polymorphisms are associated with depression, platelet aggregation and adverse cardiac events among coronary artery disease (CAD) patients. The short allele of the 5-HTTLPR polymorphism reduces transcription efficiency for the gene. However, association of 5-HTTLPR polymorphisms with adverse CV events in women with suspected ischemia has not been reported. We hypothesized an association of 5-HTTLPR polymorphism with risk for adverse CV events in women with suspected myocardial ischemia from the WISE.
Method: We genotyped 356 Caucasian women (mean age 58; 34% obstructive CAD) with suspected ischemia for the long (L) or short (S) variant of the 5-HTTLPR polymorphism. We compared the incidence of adverse CV events (first occurrence of death, myocardial infarction, stroke, or heart failure hospitalization) in genotype groups.
Results: After 5.9 years, 44 women had adverse CV events. After adjustment for age, CAD, and other risk factors, women with SS genotype were at higher risk for events vs. LL genotype (HR 4.00, 95%CI 1.38-11.59, p=0.01; LS vs LL HR 2.60, 95%CI 0.99-6.84, p=0.05). The cumulative hazard over time was significantly higher in these women with SS genotype vs. LL genotype (logrank test p=0.04). This was not linked with a significant increase in Beck depression score.
Conclusion: In this analysis, SS genotype of serotonin transporter gene polymorphism is associated with increased cardiac events in women with suspected ischemia. These results differ from previous associations of LL genotype with adverse cardiac events in men. Genotype evaluation in Caucasian women with suspected ischemia could improve risk assessment and warrant further investigation. Figure. Cumulative hazard ratios for adverse CV events by genotype in Caucasian women.
- © 2010 by American Heart Association, Inc.