title: Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation.
abstract: 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 × 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 × 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.
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. adam.leventhal@usc.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Leventhal
authors.forename: S P
authors.initials: SP
authors.lastname: David
authors.forename: M
authors.initials: M
authors.lastname: Brightman
authors.forename: D
authors.initials: D
authors.lastname: Strong
authors.forename: J E
authors.initials: JE
authors.lastname: McGeary
authors.forename: R A
authors.initials: RA
authors.lastname: Brown
authors.forename: E E
authors.initials: EE
authors.lastname: Lloyd-Richardson
authors.forename: M
authors.initials: M
authors.lastname: Munafò
authors.forename: G R
authors.initials: GR
authors.lastname: Uhl
authors.forename: R
authors.initials: R
authors.lastname: Niaura
mesh_terms: D000328:Adult; D016642:Bupropion / Q000494:pharmacology / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012907:Smoking / Q000188:drug therapy / Q000235:genetics*; D016540:Smoking Cessation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D050638:Receptors, Dopamine D4