title: Catechol-O-methyltransferase (COMT) gene variants predict response to bupropion therapy for tobacco dependence.
abstract: BACKGROUND
  Although bupropion is efficacious for smoking cessation, only a minority of smokers are able to quit. Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers. We investigated variants in the catechol-O-methyltransferase (COMT) gene in a smoking cessation trial of bupropion.
  
  
  METHODS
  A double-blind, placebo-controlled, 10-week trial of bupropion and counseling (with a 6-month follow-up period) was conducted at two university-based smoking cessation research programs. Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date.
  
  
  RESULTS
  At the end of the treatment phase, statistically significant interaction effects indicated that COMT haplotypes of two SNPs (rs737865 and rs165599) predicted the efficacy of bupropion compared with placebo. This interaction effect was attenuated at 6-month follow-up.
  
  
  CONCLUSIONS
  COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation. European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment. Small numbers of some COMT haplotypes limit interpretation of response. If study findings are confirmed in additional large studies, COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation.
authors.affiliation: Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA. wadeb@mail.med.upenn.edu
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: Leonard
authors.initials: L
authors.lastname: Epstein
authors.forename: Stephanie
authors.initials: S
authors.lastname: Restine
authors.forename: Larry
authors.initials: L
authors.lastname: Hawk
authors.forename: Peter
authors.initials: P
authors.lastname: Shields
authors.forename: Ray
authors.initials: R
authors.lastname: Niaura
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000328:Adult; D016642:Bupropion / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D016009:Chi-Square Distribution; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D002394:Catechol O-Methyltransferase