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The CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with reduced CYP3A4 protein level and function in human liver microsomes
http://hdl.handle.net/2297/39142
http://hdl.handle.net/2297/39142a548dd8f-0559-4b7f-bfbc-31ea0647826b
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
PH-PR-SHIMADA-T-349.pdf (479.0 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-10-05 | |||||
| タイトル | ||||||
| タイトル | The CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with reduced CYP3A4 protein level and function in human liver microsomes | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Okubo, Maho
× Okubo, Maho× Murayama, Norie× Shimizu, Makiko× Shimada, Tsutomu× Guengerich, F. Peter× Yamazaki, Hiroshi |
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| 書誌情報 |
Journal of Toxicological Sciences 巻 38, 号 3, p. 349-354, 発行日 2013-06-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0388-1350 | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 10.2131/jts.38.349 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.2131/jts.38.349 | |||||
| 出版者 | ||||||
| 出版者 | 日本毒性学会 = Japanese Society of Toxicological Sciences | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 権利 | ||||||
| 権利情報 | Copyright © 2013 The Japanese Society of Toxicology 日本毒性学会 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.jstage.jst.go.jp/browse/jts | |||||
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| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.jsot.jp/ | |||||
