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), ex...

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Bibliographic Details
Published in:Drug and alcohol dependence 2007-06, Vol.89 (1), p.24-33
Main Authors: Mwenifumbo, Jill C, Sellers, Edward M, Tyndale, Rachel F
Format: Article
Language:English
Subjects:
Addictive behaviors
Adolescent
Adult
Adult and adolescent clinical studies
African Continental Ancestry Group - genetics
Age Factors
Alcohol and nicotine
Area Under Curve
Aryl Hydrocarbon Hydroxylases - genetics
Biological and medical sciences
Black African descent
Black people
Cannabis
Cotinine - analogs & derivatives
Cotinine - pharmacokinetics
Cytochrome P-450 CYP2A6
Drug addiction
Female
Gender
Gender differences
Genetic Variation - genetics
Humans
Male
Marijuana
Medical sciences
Metabolic Clearance Rate - genetics
Metabolism
Middle Aged
Mixed Function Oxygenases - genetics
Nicotine
Nicotine - pharmacokinetics
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Reference Values
Sex Factors
Smoking
Smoking - blood
Smoking - ethnology
Smoking - genetics
Tobacco smoking
Tobacco, tobacco smoking
Toxicology
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Summary: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 ≤ 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.
ISSN:0376-8716
1879-0046
DOI:10.1016/j.drugalcdep.2006.11.012