Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation

Smokers (10 cigarettes per day, N331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)1.31, P0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR1.06, P0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P0.01) and in analyses predicting continuous abstinence (P's0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.