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, Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Department of Public Health, Wakayama Medical University School of Medicine, Wakayama, Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo
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.
