The CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with reduced CYP3A4 protein level and function in human liver microsomes
スポンサーリンク
概要
- 論文の詳細を見る
Effects of the CYP3A4 intron 6 C>T (CYP3A4*22) polymorphism, which has recently been reported to have a critical role in vivo, were investigated by measuring CYP3A4 protein expression levels and CYP3A4-dependent drug oxidation activities in individual human liver microsomes in vitro. Prior to protein analysis, analysis of DNA samples indicated that 36 Caucasian subjects were genotyped as CYP3A4*1/*1 and five subjects were CYP3A4*1/*22, with a CYP3A4*22 allelic frequency of 6.1%. No CYP3A4*22 alleles were found in the Japanese samples (106 alleles). Individual differences in CYP2D6-dependent dextromethorphan O-demethylation activities in liver microsomes from Caucasians were not affected by either the CYP3A4*1/*22 or CYP3A5*1/*3 genotype. Liver microsomes genotyped as CYP3A4*1/*22 (n = 4) showed significantly lower CYP3A-dependent dextromethorphan N-demethylation, midazolam 1′-hydroxylation, and testosterone 6β-hydroxylation activities, as well as lower expression levels of CYP3A protein (28% of control), compared with those of the CYP3A4*1/*1 group (n = 19). The other polymorphism, CYP3A5*1/*3, did not show these differences (n = 4). The CYP3A4*22 polymorphism was associated with reduced CYP3A4 protein expression levels and resulted in decreased CYP3A4-dependent activities in human livers. The present results suggest an important role of low expression of CYP3A4 protein associated with the CYP3A4*22 allele in the individual differences in drug clearance.
- 一般社団法人 日本毒性学会の論文
一般社団法人 日本毒性学会 | 論文
- No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats
- Genotoxicity evaluation of chlorpyrifos: a gender related approach in regular toxicity testing
- Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ9-tetrahydrocannabinol in human breast cancer cells
- Increased production of reactive oxygen species by the vacuolar-type (H+)-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells
- Evaluation of cytotoxic potential of cored soft contact lenses with adsorbed active ingredients from over-the-counter eye drops