Polymorphisms in the promoter region of the human class II alcohol dehydrogenase (ADH4) gene affect both transcriptional activity and ethanol metabolism in Japanese subjects

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概要

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• 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 0.4g/kg body weight alcohol ingestion were analyzed. When analyzed based on aldehyde dehydrogenase-2 gene (ALDH2) ^<487>Glu/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 ^<487>Glu/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.

• 日本トキシコロジー学会の論文
• 2009-02-01

著者

• FUKUNAGA Tatsushige

  Tokyo Medical Examiner's Office, Tokyo Metropolitan Government

• ABE Shuntaro

  Department of Forensic Medicine, The Jikei University School of Medicine

• NISHIMURA Fusae

  Department of Hygiene, Kanazawa University School of Medicine and Graduate School of Medical Science

• KIMURA Yukiko

  Department of Hygiene, Kanazawa University School of Medicine and Graduate School of Medical Science

• Nishimura Fusae

  Department Of Hygiene Kanazawa University School Of Medicine And Graduate School Of Medical Sciences

• Nishimura Fusae

  金沢大学 医学系研究科衛生学

• Kimura Yukiko

  Department Of Cardiology Dokkyo University School Of Medicine Koshigaya Hospital

• Kimura Yukiko

  Department Of Hygiene Kanazawa University School Of Medicine And Graduate School Of Medical Sciences

• Abe Shuntaro

  金沢大学 医学系研究科衛生学

• Abe Shuntaro

  Department Of Forensic Medicine The Jikei University School Of Medicine

• Abe Shuntaro

  Department Of Forensic Medicine Jikei University School Of Medicine

• Fukunaga Tatsushige

  金沢大学 医学系研究科衛生学

• Fukunaga Tatsushige

  Tokyo Medical Examiner's Office Tokyo Metropolitan Government

• SAIJOH Kiyofumi

  Department of Hygiene, Kanazawa University School of Medicine and Graduate School of Medical Science

• Tanii Hideji

  Department of Hygiene, Kanazawa University Graduate School of Medical Science

• Saijoh K

  Kanazawa Univ. School Of Medicine Kanazawa Jpn

• Saijoh Kiyofumi

  金沢大学 医学系研究科衛生学

• Saijoh Kiyofumi

  Department Of Hygiene Kanazawa University School Of Medicine And Graduate School Of Medical Sciences

• Saijoh Kiyofumi

  金沢大学 衛生

• Saijoh Kiyofumi

  Department Of Environmental And Molecular Bio-informatics Kanazawa University School Of Medicine

• Tanii Hideji

  金沢大学 医学系研究科衛生学

• Tanii Hideji

  Department Of Hygiene Kanazawa University Graduate School Of Medical Science

• Tanii H

  Department Of Hygiene Kanazawa University School Of Medicine

• Tanii Hideji

  Department Of Environmental And Molecular Bio-informatics Kanazawa University School Of Medicine

• Fukunaga Tatsushige

  Tokyo Medical Examiner's Office

• Sumino Kimiaki

  Osaka Occupational Health Service Center Japan Industrial Safety And Health Association

• Tanii Hisashi

  Mie Univ. Mie Jpn

• Fukunaga Tatsushige

  Tokyo Medical Examiner's Office, Tokyo Metropolitan Government

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