Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence

Clin Pharmacol Ther. 2005 Mar;77(3):145-58. doi: 10.1016/j.clpt.2004.10.011.


Nicotine is the primary addictive compound in tobacco smoke. In this review we summarize nicotine dependence and the genetics of smoking in brief before focusing on cytochrome P450 (CYP) 2A6. In humans nicotine is mainly inactivated to cotinine and CYP2A6 mediates approximately 90% of this conversion. Some, but not all, studies suggest that genetic variation in CYP2A6 may play a role in smoking. We review some of the recent findings on the influence of CYP2A6 genetic polymorphisms on nicotine kinetics, smoking behaviors, and how the gene appears to exert differential effects during various stages of smoking (eg, initiation, conversion to dependence, amount smoked during dependence, and quitting). These new findings will be put in the context of the discrepancies found in the literature. Implications of these recent findings on current and novel treatment approaches for smoking cessation and tobacco-related lung cancer will also be discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Canada / ethnology
  • Cytochrome P-450 CYP2A6
  • Health Behavior*
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Nicotine / administration & dosage
  • Nicotine / metabolism
  • Nicotine / pharmacokinetics
  • Polymorphism, Genetic
  • Smoking / genetics
  • Smoking / metabolism
  • Smoking / psychology*
  • Tobacco Use Disorder / genetics
  • Tobacco Use Disorder / metabolism
  • Tobacco Use Disorder / psychology*


  • Nicotine
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6