Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH1(2)) with the disease.
Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH1(2)) with the disease.
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DOI：
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发表时间：
1988-11
影响因子：
9.8
通讯作者：
A. Shibuya;Akira Yoshida
中科院分区：
文献类型：
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作者：
A. Shibuya;Akira Yoshida
两种主要酒精代谢酶的遗传多态性，I类醇脱氢酶同工酶之一（ADH 2）和线粒体醛脱氢酶（ALDH 2）-存在于日本人和其他东方人中，但不存在于高加索人中。约90%的东方人的肝脏ADH活性远高于大多数白人，而约50%的东方人缺乏ALDH 2活性。这种遗传差异与在东方人中观察到的酒精敏感性的高发病率有关。我们确定，通过基因组DNA样品与等位基因特异性合成寡核苷酸探针杂交，基因型的ADH 2和ALDH 2基因座的日本酒精性肝病和对照组。ADH 2基因型在患者组和对照组之间差异无统计学意义。两组间ALDH 2基因座存在显著的遗传差异。在对照组中，典型（高加索型）ALDH 1（2）基因的频率为0.65，非典型（东方型）ALDH 2（2）基因的频率为0.35，而在患者中，这些频率分别为0.93和0.07。因此，大多数（23例中的20例）日本患者为纯合子白人ALDH 1（2）/ALDH 1（2）型，仅3例为杂合子ALDH 1（2）/ALDH 2（2）型，无一例患者为纯合子东方ALDH 2（2）/ALDH 2（2）型。结果表明，具有非典型ALDH 2（2）等位基因的日本人发生酒精性肝病的风险比具有纯合子、普通型（高加索型）ALDH 1（2）/ALDH 1（2）的日本人低得多，这可能是由于他们对酒精中毒的敏感性。
Genetic polymorphisms of two major alcohol-metabolizing enzymes-i.e., one of the class I alcohol dehydrogenase isozymes (ADH2) and the mitochondrial aldehyde dehydrogenase (ALDH2)-exist in Japanese and other Orientals but not in Caucasians. Liver ADH activity of about 90% of Orientals is much higher than that of most Caucasians, while approximately 50% of Orientals lack the ALDH2 activity. The genetic differences have been implicated in the high incidence of alcohol sensitivity observed in Orientals. We determined, by means of hybridization of genomic DNA samples with allele-specific synthetic oligonucleotide probes, genotypes of the ADH2 and the ALDH2 loci of Japanese with alcoholic liver diseases and of control subjects. No significant difference between the patient and control groups was found in the ADH2 genotypes. A remarkable genetic difference between the two groups was found in the ALDH2 locus. The frequency of the typical (Caucasian-type) ALDH1(2) gene was found to be .65 and that of the atypical (Oriental type) ALDH2(2) gene was .35 in the controls, while these were .93 and .07, respectively, in the patients. Thus, most (20 of 23) of the Japanese patients were homozygous Caucasian type ALDH1(2)/ALDH1(2), only three were heterozygous ALDH1(2)/ALDH2(2), and none of the patients were homozygous Oriental type ALDH2(2)/ALDH2(2). The results indicate that Japanese with the atypical ALDH2(2) allele are at a much lower risk in developing the alcoholic liver diseases than are those with homozygous, usual (Caucasian-type) ALDH1(2)/ALDH1(2), presumably owing to their sensitivity to alcohol intoxication.