Different Effects of Polymorphic Flavin-Containing Monooxygenase 3 and Cytochrome P450 2A6 Activities on an Index of Arteriosclerosis as a Lifestyle-Related Disease in a General Population in Japan

Title:Different Effects of Polymorphic Flavin-Containing Monooxygenase 3 and Cytochrome P450 2A6 Activities on an Index of Arteriosclerosis as a Lifestyle-Related Disease in a General Population in Japan

Volume: 21 Issue: 14

Author(s): Mirai Uraoka, Makiko Shimizu, Yoshiki Kuwajima, Ami Mizugaki, Haruka Yokoyama, Kanae Mure and Hiroshi Yamazaki*

Affiliation:

• Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo,Japan

Keywords: Ankle-brachial pressure index ABI score, FMO3, CYP2A6, P450 2A6, genotype, phenotype.

Abstract: Background: The relationships between lifestyle-related diseases and polymorphic drug-metabolizing enzyme activities in the general population in Japan remain unclear.

Objective: In this study, the relationships between an index of arteriosclerosis and the phenotypic activities of flavin-containing monooxygenase 3 (FMO3) and cytochrome P450 (P450) 2A6 were analysed.

Methods: Subjects in a general population in Japan (age range 35-97 years, 640 men and 795 women, 12% were current smokers) who took part in a health check program were recruited.

Results: Subjects were divided into two groups using the median ankle-brachial pressure index (ABI) score. Subjects harbouring P450 2A6 wild-type allele had a significant age-adjusted odds ratio of 1.3 (95% CI, 1.0-1.6) of having a lower than median ABI score compared with subjects for mutant P450 2A6. For subjects with wild-type FMO3, the odds ratio of 0.89 was not significant. The proportions of P450 2A6 extensive metabolizers varied significantly across the inter-quartile ranges of the ABI scores (p = 0.008). Furthermore, the proportion of subjects with low ABI scores was also dependent on the phenotypic P450 2A6 activity (p = 0.025) as estimated from the P450 2A6 genotype. These results suggest that in a general population in Japan, the ABI score, as a risk index for arteriosclerosis, is associated with the predicted P450 2A6 phenotype but is not associated with FMO3 function.

Conclusion: The P450 2A6 wild-type allele may be a possible candidate biomarker for arteriosclerosis in a general population in Japan with a variety of dietary habits.

Cite this article as:

Uraoka Mirai , Shimizu Makiko , Kuwajima Yoshiki , Mizugaki Ami , Yokoyama Haruka , Mure Kanae and Yamazaki Hiroshi*, Different Effects of Polymorphic Flavin-Containing Monooxygenase 3 and Cytochrome P450 2A6 Activities on an Index of Arteriosclerosis as a Lifestyle-Related Disease in a General Population in Japan, Current Drug Metabolism 2020; 21 (14) . https://dx.doi.org/10.2174/1389200221666201009140802

DOI https://dx.doi.org/10.2174/1389200221666201009140802	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453