title: No evidence for a major role of polymorphisms during bupropion treatment.
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.
authors.affiliation: Department of Biostatistics, Section on Statistical Genetics, Ryals Public Health Building, Suite 327, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Hu
authors.forename: David T
authors.initials: DT
authors.lastname: Redden
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Restine
authors.forename: Angela
authors.initials: A
authors.lastname: Pinto
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
mesh_terms: D000328:Adult; D016642:Bupropion / Q000009:adverse effects* / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016540:Smoking Cessation / Q000379:methods*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
chemical_list: D018765:Dopamine Uptake Inhibitors; D016642:Bupropion