管理No.20171206-01(Original work)The Cytochrome P450(CYP)3A4, CYP3A5 Genotype and Phenotype Frequencies and that Novel Single Polymorphisms affected Phenotype from Japanese Individual

管理No 20171206-01
受付日 2017年11月29日
受理日 2017年12月6日
論文の種類 Original work(原著)
著者名 Makoto NAGAI1, Kazuhiro INAGAKI2

Department of Medical Technology, School of Health Sciences, Gifu University of Medical Science1

Department of Pharmacy, Mejou University2

論文(電子版) No.AC20171206-01
キーワード CYP3A4, CYP3A5, single nucleotides polymorphisms, CYP3A activity ratio
掲載 医療看護環境学
Medical Nursing Environment Science
Vol.1,No.1,Page.11-17,(11-17)

Summary

Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play important roles in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study investigated the effect of CYP3A4 and CYP3A5 genetic polymorphisms and CYP3A combined genotypes on CYP3A metabolic activity in healthy Japanese.
Urine samples were collected from 183 healthy volunteers. The rate of 6β-hydroxycortisol and free cortisol in urine has been employed as an endogenous measure of CYP3A activity. DNA samples were obtained from urine samples of 53 healthy volunteers. Allele genotyping was carried out by polymerase chain reaction (PCR) and DNA sequencing.
The CYP3A activity ratio showed a normal distribution. About 106 activity differences of steroid metabolism were indicated. The frequencies of CYP3A4*2, *2/*5, *5, *18 and CYP3A5*1/*3, *3/*3 variant alleles in Japanese are found at frequencies of 5.7%, 1.9%, 3.8%, 1.9% and 37.7%, 47.2%, respectively.
The CYP3A genotype contributes slightly to explaining the variability between patients in cortisol metabolism, however, the effect is small.

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