title: Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers.
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M K
authors.initials: MK
authors.lastname: Ho
authors.forename: J C
authors.initials: JC
authors.lastname: Mwenifumbo
authors.forename: N
authors.initials: N
authors.lastname: Al Koudsi
authors.forename: K S
authors.initials: KS
authors.lastname: Okuyemi
authors.forename: J S
authors.initials: JS
authors.lastname: Ahluwalia
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D015992:Body Mass Index; D003367:Cotinine / Q000031:analogs & derivatives / Q000097:blood; D065637:Cytochrome P-450 CYP2A6; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism*; D011110:Polymorphism, Genetic; D016540:Smoking Cessation
chemical_list: C001381:hydroxycotinine; D009538:Nicotine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine