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人类肝脏酒精脱氢酶和乙醛脱氢酶:基因多态性与活性

Human hepatic alcohol and aldehyde dehydrogenases: genetic polymorphism and activities.

作者信息

Yao C T, Liao C S, Yin S J

机构信息

Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan, R.O.C.

出版信息

Proc Natl Sci Counc Repub China B. 1997 Jul;21(3):106-11.

PMID:9309874
Abstract

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for the metabolism of ethanol in the body. Both exhibit genetic polymorphism in racial populations. To determine hepatic ethanol metabolizing activities in relation to genetic polymorphism, a total of 23 surgical specimens were investigated. The expression patterns of ADH and ALDH isoenzymes were identified by means of agarose isoelectric focusing, and the activities were assayed spectrophotometrically. At 33 mM ethanol, pH 7.5, the activities in the liver with the homozygous phenotype ADH2 1-1 and ADH2 2-2 and the heterozygous phenotype ADH2 1-2 were determined to be 2.9 +/- 0.7, 16.0 +/- 2.5, and 13.6 +/- 1.0 U/g tissue, respectively. The activities of the ALDH2-active and ALDH2-inactive phenotypes at 200 microM acetaldehyde were determined to be 1.06 +/- 0.13 and 0.71 +/- 0.07 U/g tissue, respectively. These findings indicate that human hepatic ethanol-metabolizing activities differ significantly with respect to polymorphism at both the ADH2 and ALDH2 loci. The results suggest that this genetically determined differential hepatic activity may influence drinking behavior and the development of alcoholism among Orientals.

摘要

酒精脱氢酶(ADH)和乙醛脱氢酶(ALDH)是体内负责乙醇代谢的主要酶。两者在不同种族人群中均表现出基因多态性。为了确定与基因多态性相关的肝脏乙醇代谢活性,共研究了23份手术标本。通过琼脂糖等电聚焦法鉴定ADH和ALDH同工酶的表达模式,并采用分光光度法测定其活性。在33 mM乙醇、pH 7.5条件下,纯合子表型ADH2 1-1和ADH2 2-2以及杂合子表型ADH2 1-2的肝脏中乙醇代谢活性分别测定为2.9±0.7、16.0±2.5和13.6±1.0 U/g组织。在200 μM乙醛条件下,ALDH2活性型和ALDH2非活性型表型的活性分别测定为1.06±0.13和0.71±0.07 U/g组织。这些发现表明,人类肝脏乙醇代谢活性在ADH2和ALDH2基因座的多态性方面存在显著差异。结果表明,这种由基因决定的肝脏活性差异可能会影响东方人的饮酒行为和酒精中毒的发生。

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Ethnic related selection for an ADH Class I variant within East Asia.东亚地区与乙醇脱氢酶I类变体相关的种族选择。
PLoS One. 2008 Apr 2;3(4):e1881. doi: 10.1371/journal.pone.0001881.
3
Alcohol dehydrogenase and alcohol dependence: variation in genotype-associated risk between populations.乙醇脱氢酶与酒精依赖:不同人群中基因型相关风险的差异
Am J Hum Genet. 2002 Nov;71(5):1247-50; author reply 1250-1. doi: 10.1086/344287.