title: Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.
abstract: OBJECTIVE
  Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes.
  
  
  METHODS
  In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment.
  
  
  RESULTS
  For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non-replication can alter the interpretation of pharmacogenetic findings.
  
  
  CONCLUSIONS
  Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, United States; The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, United States. Electronic address: chenli@psychiatry.wustl.edu.
authors.forename: Li-Shiun
authors.initials: LS
authors.lastname: Chen
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53711, United States.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Baker
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53711, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Jorenby
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53711, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Piper
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.affiliation: Division of Health, Social and Economic Research, Research Triangle Institute International, Research Triangle Park, NC, 27709, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Johnson
authors.affiliation: Department of Epidemiology, Michigan State University, East Lansing, MI, 48824, United States.
authors.forename: Naomi
authors.initials: N
authors.lastname: Breslau
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, United States.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hatsukami
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carney
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, United States; The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, United States.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000188:drug therapy*; D016540:Smoking Cessation / Q000379:methods*; D061485:Tobacco Use Cessation Devices; D016896:Treatment Outcome; D000068580:Varenicline / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D000068580:Varenicline
keywords: CHRNA5; Nicotine replacement therapy; Smoking cessation; Varenicline; pharmacogenetic