Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers

M. K. Ho, J. C. Mwenifumbo, N. Al Koudsi, K. S. Okuyemi, J. S. Ahluwalia, N. L. Benowitz, R. F. Tyndale

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)635-643
Number of pages9
JournalClinical pharmacology and therapeutics
Volume85
Issue number6
DOIs
StatePublished - Jun 2009

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