Nicotine metabolism and CYP2A6 activity in a population of black African descent: impact of gender and light smoking.
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.
Mwenifumbo
Jill C
JC
The Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Canada M5S 1A8.
Sellers
Edward M
EM
Tyndale
Rachel F
RF
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*
C001381:hydroxycotinine; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine