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Polymorphisms in the promoter region of the human class II alcohol dehydrogenase (ADH4) gene affect both transcriptional activity and ethanol metabolism in Japanese subjects
http://hdl.handle.net/2297/46567
http://hdl.handle.net/2297/465672ae25469-d5bc-4ebf-a964-d9cf7311bc36
名前 / ファイル | ライセンス | アクション |
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ME-PR-TANII-H-89.pdf (167.4 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-03 | |||||
タイトル | ||||||
タイトル | Polymorphisms in the promoter region of the human class II alcohol dehydrogenase (ADH4) gene affect both transcriptional activity and ethanol metabolism in Japanese subjects | |||||
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 |
Kimura, Yukiko
× Kimura, Yukiko× Nishimura, Fusae T.× Abe, Shuntaro× Fukunaga, Tatsushige× Tanii, Hideji× Saijoh, Kiyofumi |
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書誌情報 |
The Journal of Toxicological Sciences 巻 34, 号 1, p. 89-97, 発行日 2009-02-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0388-1350 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA11508363 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.2131/jts.34.89 | |||||
出版者 | ||||||
出版者 | 日本毒性学会 = Japanese Society of Toxicology | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Class II alcohol dehydrogenase (π-ADH), encoded by alcohol dehydrogenase (ADH4), is considered to contribute to ethanol (EtOH) oxidation in the liver at high concentration. Four single nucleotide polymorphisms (SNPs) were found in the promoter region of this gene. Analysis of genotype distribution in 102 unrelated Japanese subjects revealed that four loci were in strong linkage disequilibrium and could be classified into three haplotypes. The effects of these polymorphisms on transcriptional activity were investigated in HepG2 cells. Transcriptional activity was significantly higher in cells with the -136A allele than in those with the -136C allele. To investigate whether this difference in transcriptional activity caused a difference in EtOH elimination, previous data on blood EtOH changes after 0.4 g/kg body weight alcohol ingestion were analyzed. When analyzed based on aldehyde dehydrogenase-2 gene (ALDH2) 487Glu/Lys genotype, the significantly lower level of EtOH at peak in subjects with -136C/A and -136A/A genotype compared with subjects with -136C/C genotype indicated that -136 bp was a suggestive locus for differences in EtOH oxidation. This effect was observed only in subjects with ALDH2 487Glu/Glu. These results suggested that the SNP at -136bp in the ADH4 promoter had an effect on transcriptional regulation, and that the higher activity of the -136A allele compared with the -136C allele caused a lower level of blood EtOH after alcohol ingestion; that is, individuals with the -136A allele may consume more EtOH and might have a higher risk for development of alcohol dependence than those without the -136A allele. | |||||
権利 | ||||||
権利情報 | Copyright © 2009 The Japanese Society of Toxicology | |||||
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 | http://www.jsot.jp/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.jstage.jst.go.jp/browse/jts |