title: Nicotine metabolism and CYP2A6 activity in a population of black African descent: impact of gender and light smoking.
abstract: Genetic variation in CYP2A6 (the main nicotine metabolizing enzyme) accounts for some, but not all, of the interindividual and interethnic variability in the rates of nicotine metabolism. We conducted a nicotine kinetic study in smokers and nonsmokers of black African descent (N=190), excluding those with common genetic variants in CYP2A6, to investigate the association of demographic variables with CYP2A6 activity (3HC/COT ratio) and nicotine disposition kinetics (estimated nicotine AUC). An additional aim was to examine whether impaired CYP2A6 activity and/or nicotine disposition kinetics were associated with lower cigarette consumption in a population of light smokers (mean<or=10 cigarettes per day). We found that smokers had decreased nicotine metabolism (p<0.05), that women had higher CYP2A6 activity (p<0.01) and that, in non-elderly adults, age did not impact CYP2A6 activity (p=0.65) or nicotine disposition kinetics (p=0.06). Our study also demonstrated that neither current alcohol use nor current marijuana use was associated with altered CYP2A6 activity (p=0.55 and 0.72, respectively) or nicotine disposition kinetics (p=0.38 and 0.91, respectively). Despite the light cigarette consumption of the smokers (N=94), higher CYP2A6 activity was associated with greater cigarette consumption (p<0.005). These findings highlight the need for smoking status and gender to be considered when interpreting studies using nicotine.
authors.affiliation: The Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Canada M5S 1A8.
authors.forename: Jill C
authors.initials: JC
authors.lastname: Mwenifumbo
authors.forename: Edward M
authors.initials: EM
authors.lastname: Sellers
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D003367:Cotinine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009538:Nicotine / Q000493:pharmacokinetics*; D012016:Reference Values; D012737:Sex Factors; D012907:Smoking / Q000097:blood / Q000208:ethnology / Q000235:genetics*
chemical_list: C001381:hydroxycotinine; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine