Prospective association of dopamine-related polymorphisms with smoking cessation in general care.
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.
Breitling
Lutz P
LP
Division of Clinical Epidemiology & Aging Research, German Cancer Research Center, Bergheimer Str 20, D-69115 Heidelberg, Germany. l.breitling@dkfz-heidelberg.de
Twardella
Dorothee
D
Hoffmann
Michael M
MM
Witt
Stephanie H
SH
Treutlein
Jens
J
Brenner
Hermann
H
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
D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D016642:Bupropion; D004299:Dopamine beta-Hydroxylase; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases