Association of Nicotine Metabolite Ratio and CYP2A6 Genotype With Smoking Cessation Treatment in African‐American Light Smokers

Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)‐metabolizing enzyme in humans. We investigated the relationships between CYP2A6 genotype, baseline plasma trans‐ 3′‐hydroxycotinine/cotinine (3HC/COT) (a phenotypic marker of CYP2A6 activity), and smoking behavior in African‐American light smokers. Cigarette consumption, age of initiation, and dependence scores did not differ among 3HC/COT quartiles or CYP2A6 genotype groups. Slow metabolizers (SMs; both genetic and phenotypic) had significantly higher plasma NIC levels, suggesting that cigarette consumption was not reduced to adjust for slower rates of NIC metabolism. Individuals in the slowest 3HC/COT quartile had higher quitting rates with both placebo and NIC gum treatments (odds ratio 1.85, 95% confidence interval (CI) 1.08–3.16, P = 0.03). Similarly, the slowest CYP2A6 genotype group had higher quitting rates, although this trend did not reach significance (odds ratio 1.61, 95% CI 0.95–2.72, P = 0.08). The determination of the 3HC/COT ratio, and possibly CYP2A6 genotype, may be useful in the future for personalizing the choice of smoking cessation treatment in African‐American light smokers. Clinical Pharmacology & Therapeutics (2009); 85 , 6, 635–643 doi: 10.1038/clpt.2009.19