Genetic variability in CYP2A6 and the pharmacokinetics of nicotine.
Nicotine is the psychoactive substance responsible for tobacco dependence. It is also a therapeutic used to aid smoking cessation. Cytochrome P450 (CYP)2A6 is the human hepatic enzyme that mediates most of nicotine's metabolic inactivation to cotinine. Genetic variation in the CYP2A6 gene can increase or decrease enzyme activity through altering the protein's expression level or its structure and function. This article reviews CYP2A6 genetic variation and its impact on in vivo nicotine kinetics, including a description of the individual variants, different phenotyping approaches for assessing in vivo CYP2A6 activity and other sources of variation in nicotine metabolism such as gender. In addition, the effect of CYP2A6 polymorphisms on smoking behavior and tobacco-related lung cancer risk are briefly described. Furthering knowledge in this area will improve interpretation of studies examining smoking behavior, as well as those using nicotine as a therapeutic agent.
Mwenifumbo
Jill C
JC
University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Tyndale
Rachel F
RF
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003367:Cotinine / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009538:Nicotine / Q000493:pharmacokinetics*; D044469:Racial Groups / Q000235:genetics; D017384:Sequence Deletion
D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine