A synergistic effect of serotonin transporter gene polymorphism and smoking in association with CHD

Serotonin induces vasoconstriction in the presence of atherosclerotic lesio ns. Platelets acquire serotonin from the extracellular space by serotonin t ransporter and release it following aggregation. There is a functional poly morphism in the serotonin transporter (5-HTT) gene promoter associated with transcriptional efficacy and plasma serotonin levels. To examine whether t he polymorphism is associated with coronary heart disease (CHD) in the Japa nese, we analyzed 144 male CHD patients with an onset age before 65 and 222 apparently healthy men. The L allele was observed significantly more frequ ently in the CHD patients (26%) than in the control subjects (19%); the odd s ratio was 1.48 (p <0.03). A significant interaction between the polymorph ism and smoking was observed for CHD (p = 0.03), suggesting that the two ha ve a synergistic effect on CHD. Odds ratio of the combination of the L alle le and smoking was 1.95 (p <0.003). The 5-HTT gene promoter polymorphism ma y play a role in susceptibility to CHD, particularly when it is combined wi th smoking.