Nicotine metabolism and CYP2A6 activity in a population of black African descent: impact of gender and light smoking.
paper
Cited
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- Authors
- Mwenifumbo, Jill C; Sellers, Edward M; Tyndale, Rachel F
- Year
- 2007
- Journal
- Drug and alcohol dependence
- PMID
- 17161559
- DOI
- 10.1016/j.drugalcdep.2006.11.012
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.
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