title: Prospective association of dopamine-related polymorphisms with smoking cessation in general care.
abstract: OBJECTIVE
  Genetic contributions to nicotine dependence have been demonstrated repeatedly, but the relevance of individual polymorphisms for smoking cessation remains controversial.
  
  
  METHODS
  We examined genotypes at two dopamine-related loci, DRD2/ANKK1 (rs1800497) and DBH (rs77905), in 577 heavy smokers participating in a prospective study of smoking cessation in general care in Germany.
  
  
  RESULTS
  Smoking status after 1 year was significantly associated with DRD2/ANKK1, odds of abstinence being 4.4-fold (95% CI: 1.5-12.9) increased in TT- versus CC-homozygous subjects (p = 0.008). No effect was observed for the DBH genotype. The smoking cessation drug bupropion appeared to be particularly effective in CC-homozygotes (among CC subjects there was a 28% higher cessation probability among those taking buproprion; among T carrier subjects there was an increase only by 12%).
  
  
  CONCLUSIONS
  The large effects observed for DRD2/ANKK1 might be related to our study design, in which individual therapy was decided by the physician. Further studies are needed to clarify the genetic effects of DRD2/ANKK1 especially in 'real-life' settings outside clinical trials.
authors.affiliation: Division of Clinical Epidemiology & Aging Research, German Cancer Research Center, Bergheimer Str 20, D-69115 Heidelberg, Germany. l.breitling@dkfz-heidelberg.de
authors.forename: Lutz P
authors.initials: LP
authors.lastname: Breitling
authors.forename: Dorothee
authors.initials: D
authors.lastname: Twardella
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000328:Adult; D000368:Aged; D016642:Bupropion / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005858:Germany; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012044:Regression Analysis; D016540:Smoking Cessation; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D016642:Bupropion; D004299:Dopamine beta-Hydroxylase; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases