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Association of Nicotine Metabolite Ratio and CYP2A6 Genotype With Smoking Cessation Treatment in African‐American Light Smokers
Author(s) -
Ho MK,
Mwenifumbo JC,
Al Koudsi N,
Okuyemi KS,
Ahluwalia JS,
Benowitz NL,
Tyndale RF
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.19
Subject(s) - cyp2a6 , cotinine , odds ratio , nicotine , confidence interval , smoking cessation , genotype , medicine , quartile , pharmacogenetics , pharmacology , physiology , genetics , biology , cyp1a2 , cytochrome p450 , pathology , metabolism , gene
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