PT  - JOURNAL ARTICLE
AU  - Hiroki Hosono
AU  - Masaki Kumondai
AU  - Masamitsu Maekawa
AU  - Hiroaki Yamaguchi
AU  - Nariyasu Mano
AU  - Akifumi Oda
AU  - Noriyasu Hirasawa
AU  - Masahiro Hiratsuka
TI  - Functional Characterization of 34 CYP2A6 Allelic Variants by Assessment of Nicotine <em>C</em>-Oxidation and Coumarin 7-Hydroxylation Activities
AID  - 10.1124/dmd.116.073494
DP  - 2017 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 279--285
VI  - 45
IP  - 3
4099  - http://dmd.aspetjournals.org/content/45/3/279.short
4100  - http://dmd.aspetjournals.org/content/45/3/279.full
SO  - Drug Metab Dispos2017 Mar 01; 45
AB  - CYP2A6, a member of the cytochrome P450 (P450) family, is one of the enzymes responsible for the metabolism of therapeutic drugs and such tobacco components as nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and N-nitrosodiethylamine. Genetic polymorphisms in CYP2A6 are associated with individual variation in smoking behavior, drug toxicities, and the risk of developing several cancers. In this study, we conducted an in vitro analysis of 34 allelic variants of CYP2A6 using nicotine and coumarin as representative CYP2A6 substrates. These variant CYP2A6 proteins were heterologously expressed in 293FT cells, and their enzymatic activities were assessed on the basis of nicotine C-oxidation and coumarin 7-hydroxylation activities. Among the 34 CYP2A6 variants, CYP2A6.2, CYP2A6.5, CYP2A6.6, CYP2A6.10, CYP2A6.26, CYP2A6.36, and CYP2A6.37 exhibited no enzymatic activity, whereas 14 other variants exhibited markedly reduced activity toward both nicotine and coumarin. These comprehensive in vitro findings may provide useful insight into individual differences in smoking behavior, drug efficacy, and cancer susceptibility.