Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans.

ABSTRACT: Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3'hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3'hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e-8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e-22, 21.8% variation explained; males: beta = 0.75, P = 1.2e-37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was fo

SUBMITTER: Chenoweth MJ 

PROVIDER: S-EPMC8486765 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature