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

Smokers (>= 10 cigarettes per day, N = 331) 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 x Treatment interaction (P = 0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR) = 1.31, P < 0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR = 1.06, P = 0.23). The Genotype x Treatment interaction remained when controlling for demographic and clinical covariates (P = 0.01) and in analyses predicting continuous abstinence (P's <= 0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches. The Pharmacogenomics Journal (2012) 12, 86-92; doi:10.1038/tpj.2010.64; published online 27 July 2010