Prospective association of dopamine-related polymorphisms with smoking cessation in general care

Pharmacogenomics. 2010 Apr;11(4):527-36. doi: 10.2217/pgs.10.1.

Abstract

Aims: Genetic contributions to nicotine dependence have been demonstrated repeatedly, but the relevance of individual polymorphisms for smoking cessation remains controversial.

Materials & 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%).

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bupropion / administration & dosage
  • Bupropion / pharmacokinetics
  • Bupropion / therapeutic use
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacokinetics
  • Dopamine Uptake Inhibitors / therapeutic use
  • Dopamine beta-Hydroxylase / genetics*
  • Germany
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Regression Analysis
  • Smoking Cessation*
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / genetics
  • Treatment Outcome

Substances

  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D2
  • Bupropion
  • Dopamine beta-Hydroxylase
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases