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.