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.