Effects upon in-vivo nicotine metabolism reveal functional variation in FMO3 associated with cigarette consumption.

ABSTRACT:

Background

Flavin-containing monooxygenases (FMO) catalyze the metabolism of nucleophilic heteroatom-containing drugs and xenobiotics, including nicotine. Rare mutations in FMO3 are responsible for defective N-oxidation of dietary trimethylamine leading to trimethylaminuria, and common genetic variation in FMO3 has been linked to interindividual variability in metabolic function that may be substrate specific.

Methods

A genetic model of CYP2A6 function is used as a covariate to reveal functional polymorphism in FMO3 that indirectly influences the ratio of deuterated nicotine metabolized to cotinine following oral administration. The association is tested between FMO3 haplotype and cigarette consumption in a set of nicotine-dependent smokers.

Results

FMO3 haplotype, ba

SUBMITTER: Bloom AJ 

PROVIDER: S-EPMC4583063 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature