Determination of Genotype Combinations That Can Predict the Outcome of the Treatment of Alcohol Dependence Using the 5-HT 3 Antagonist Ondansetron

ObjectiveThe authors previously reported that the 5′-HTTLPR-LL and rs1042173-TT (SLC6A4-LL/TT) genotypes in the serotonin transporter gene predicted a significant reduction in the severity of alcohol consumption among alcoholics receiving the 5-HT3 antagonist ondansetron. In this study, they explored additional markers of ondansetron treatment response in alcoholics by examining polymorphisms in the HTR3A and HTR3B genes, which regulate directly the function and binding of 5-HT3 receptors to ondansetron.MethodThe authors genotyped one rare and 18 common single-nucleotide polymorphisms in HTR3A and HTR3B in the same sample that they genotyped for SLC6A4-LL/TT in the previous randomized, double-blind, 11-week clinical trial. Participants were 283 European Americans who received oral ondansetron (4 µg/kg of body weight twice daily) or placebo along with weekly cognitive-behavioral therapy. Associations of individual and combined genotypes with treatment response on drinking outcomes were analyzed.ResultsIndi...