Influence of serotonin transporter gene polymorphism on depressive symptoms and new cardiac events after acute myocardial infarction

Background: In patients with acute myocardial infarction (AMI), depressive symptoms increase the risk for cardiac events. Recently, the S allele of the serotonin transporter (5-HTT) gene-linked polymorphic region was shown to reduce transcription of this gene and thus reduce serotonin reuptake, and this allele is linked with depressive symptoms as well as other psychiatric diseases. However, the influence of the S allele on depressive symptoms and cardiac events after AMI is unclear. Methods: To investigate whether the S allele was associated with depressive symptoms and cardiac events after AMI, we prospectively examined depressive symptoms and new cardiac events in 2509 genotyped patients with AMI. Results: Depressive symptoms were more common in patients with the S allele than in those without it (48.3% vs 35.0%, P = .02). Multivariate analysis revealed that the S allele was independently associated with depressive symptoms (odds ratio 2.19, 95% confidence interval [CI] 1.21-3.98, P = .01). Cardiac events (cardiac death, revascularization, heart failure, reinfarction, arrhythmia, and unstable angina) were more frequent in patients with the S allele than in those without it (31.3% vs 22.3%, P = .046). Multivariate Cox regression analysis revealed an association between the S allele and an increased risk for cardiac events (hazard ratio [HR] 1.69, 95% CI 1.03-2.78, P = .04). However, the HR became insignificant after an adjustment for depressive symptoms (HR 1.30, 95% CI 0.84-2.01, P = .24). Conclusions: The S allele in the 5-HTT gene-linked polymorphic region is associated with an increased risk for subsequent cardiac events, which is mediated, at least in part, by the depressive symptoms in patients after AMI.