Meta‐analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence

Abstract

The neurotransmitter serotonin (5‐HT) has been shown to regulate alcohol consumption in both animals and humans. Since activity of the 5‐HT transporter protein (5‐HTT) regulates 5‐HT levels, the gene encoding this protein may contribute to the risk of alcohol dependence (AD). Studies of the association to AD of a functional insertion‐deletion polymorphism in the 5‐HTT‐linked promoter region (5‐HTTLPR) have yielded inconsistent results. We conducted a meta‐analysis of data from 17 published studies (including 3,489 alcoholics and 2,325 controls) investigating the association between 5‐HTTLPR alleles and AD. The frequency of the short (S) allele at 5‐HTTLPR was significantly associated with AD [odds ratio (OR) = 1.18, 95% CI = 1.03–1.33). Moreover, a greater association with the S allele was seen among individuals with AD complicated by either a co‐morbid psychiatric condition or an early‐onset or more severe AD subtype [OR = 1.34 (95% CI = 1.11–1.63)]. Allelic variation at 5‐HTTLPR contributes to risk for AD, with the greatest effect observed among individuals with a co‐occurring clinical feature. © 2004 Wiley‐Liss, Inc.