ABSTRACT
This study evaluated the ability of polymorphisms in five candidate genes to predict weight gain among patients taking bupropion or placebo in a smoking cessation trial. Five hundred fifty-three smokers were enrolled into a randomized double-blind, placebo-controlled trial and followed for 12 months. Five candidate genes [DRD2 Taq1 (rs1800497), DRD2-141 (rs1799732), C957T (rs6277), COMT (rs4818), and SLC6A3] were genotyped. Weights at baseline, at end of treatment, and after 6 and 12 months of follow-up were self-reported. Smoking abstinence at each endpoint was self-reported and confirmed biochemically. A self-reported average weight gain after 12 months of 1.1 +/- 6.0 kg (mean +/- standard deviation) in the bupropion group and 1.8 +/- 4.8 kg in the placebo group was noted. For subjects with biochemically confirmed abstinence from smoking, the HL genotype (alleles coding Val at codon 108 are denoted as H, and those coding Met are denoted as L) at the COMT locus and A1A1 genotype at the DRD2 Taq1 locus were associated with less weight gain at the end of treatment. The TC genotype at the C957T locus was associated with increased weight gain at 6 months of follow-up. However, no polymorphisms or their interactions with bupropion consistently and significantly predicted baseline BMI or weight change during treatment for all study subjects. Overall, our results do not support a major role for these five candidate genes in weight gain after smoking cessation.
Subject(s)
Bupropion/adverse effects , Dopamine Uptake Inhibitors/adverse effects , Obesity/genetics , Polymorphism, Genetic , Smoking Cessation/methods , Adult , Bupropion/therapeutic use , Dopamine Uptake Inhibitors/therapeutic use , Double-Blind Method , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Pharmacogenetics , Treatment Outcome , Weight Gain/drug effects , Weight Gain/geneticsABSTRACT
RATIONALE: Despite the high prevalence and public health significance of weight gain following smoking cessation, little is known about the underlying bio-behavioral mechanisms or effective therapies. OBJECTIVES: We evaluated the effects of bupropion on food reward following smoking abstinence and the moderating influence of genotype. METHODS: Seventy-one smokers of European ancestry were genotyped for the dopamine D2 receptor ( DRD2) Taq1 polymorphism and randomized to treatment with bupropion (300 mg) or placebo for smoking cessation. Subjects participated in two behavioral laboratory sessions during which the rewarding value of food was assessed using a behavioral economics measure: session 1 occurred prior to medication and before cessation of smoking; session 2 occurred following 3 weeks of medication and 1 week of sustained abstinence. RESULTS: Carriers of the DRD2 A1 minor allele exhibited significant increases in the rewarding value of food following abstinence from smoking, and these effects were attenuated by bupropion treatment ( P=0.03 for medication by genotype interaction). Further, higher levels of food reward at session 2 (post-quit) predicted a significant increase in weight by 6-month follow-up in the placebo group, but not in the bupropion-treated group ( P=0.006 for medication by food reward interaction). CONCLUSIONS: These results provide new evidence that the increase in body weight that occurs following smoking cessation is related to increases in food reward, and that food reward is partly determined by genetic factors. Bupropion's efficacy in attenuating abstinence-induced weight gain may be attributable, in part, to decreasing food reward.
