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日本男性乙醛脱氢酶2(ALDH2)基因多态性与酒精-血压关系

Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship.

作者信息

Tsuritani I, Ikai E, Date T, Suzuki Y, Ishizaki M, Yamada Y

机构信息

Department of Hygiene, Kanazawa Medical University, Ishikawa, Japan.

出版信息

Am J Hypertens. 1995 Nov;8(11):1053-9. doi: 10.1016/0895-7061(95)00222-B.

Abstract

Aldehyde dehydrogenase with a low Michaelis constant (Km), ALDH2, is a major enzyme involved in the conversion of acetaldehyde, a toxic metabolite of ethanol, into acetic acid in the liver. Inherited deficiency of ALDH2 activity is found in half of Japanese, and is characterized by "Oriental flushing" after alcohol consumption. The aim of the present study is to evaluate the influence of the genetic polymorphism in alcohol metabolism on the sensitivity to the pressor effect of alcohol. Genotypes of ALDH2 were determined in 403 middle-aged Japanese men using genomic DNA extracted from white blood cells. Two hundred and forty-three (60%) of the subjects were shown to be homozygotes for the normal ALDH2 gene, 25 (6%) of the subjects were homozygotes for the mutant ALDH2 gene, and the remaining 135 (33%) were heterozygotes. None of the homozygotes for the mutant gene drank enough to show the pressor effect of alcohol. Elevations of blood pressure associated with increasing alcohol consumption or with elevations of serum gamma-glutamyl transpeptide (GTP) level were not different between the other two ALDH2-genotypes. It can be concluded that polymorphism in the ALDH2-genotype found in Japanese men does not affect the individual sensitivity to the pressor effect of alcohol.

摘要

米氏常数(Km)较低的乙醛脱氢酶ALDH2是肝脏中参与将乙醇的有毒代谢产物乙醛转化为乙酸的主要酶。在半数日本人中发现存在遗传性ALDH2活性缺乏,其特征是饮酒后出现“东方潮红”。本研究的目的是评估酒精代谢中的基因多态性对酒精升压作用敏感性的影响。使用从白细胞中提取的基因组DNA,对403名中年日本男性的ALDH2基因型进行了测定。结果显示,243名(60%)受试者为正常ALDH2基因的纯合子,25名(6%)受试者为突变型ALDH2基因的纯合子,其余135名(33%)为杂合子。突变基因纯合子中无人饮酒量足以表现出酒精的升压作用。在其他两种ALDH2基因型之间,与饮酒量增加或血清γ-谷氨酰转肽酶(GTP)水平升高相关的血压升高并无差异。可以得出结论,日本男性中发现的ALDH2基因型多态性不会影响个体对酒精升压作用的敏感性。

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