Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain.

ABSTRACT: A common haplotype of the flavin-containing monooxygenase gene FMO3 is associated with aberrant mRNA splicing, a twofold reduction in in vivo nicotine N-oxidation and reduced nicotine dependence. Tobacco remains the largest cause of preventable mortality worldwide. CYP2A6, the primary hepatic nicotine metabolism gene, is robustly associated with cigarette consumption but other enzymes contribute to nicotine metabolism. We determined the effects of common variants in FMO3 on plasma levels of nicotine-N-oxide in 170 European Americans administered deuterated nicotine. The polymorphism rs2266780 (E308G) was associated with N-oxidation of both orally administered and ad libitum smoked nicotine (P⩽3.3 × 10^-5 controlling for CYP2A6 genotype). In vitro, the FMO3 G308 variant was not as

SUBMITTER: Teitelbaum AM 

PROVIDER: S-EPMC5599305 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature