Thomasson H R, Crabb D W, Edenberg H J, Li T K, Hwu H G, Chen C C, Yeh E K, Yin S J
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Alcohol Clin Exp Res. 1994 Jun;18(3):640-3. doi: 10.1111/j.1530-0277.1994.tb00923.x.
Genetic variation at two polymorphic alcohol dehydrogenase loci, ADH2 and ADH3, and at the polymorphic mitochondrial aldehyde dehydrogenase locus, ALDH2, may influence the risk of developing alcoholism by modulating the rate of elimination of ethanol and the rate of formation and elimination of acetaldehyde. Populations differ in allele frequencies at these loci. We determined the genotypes at all three of these loci in Atayal natives of Taiwan. The frequencies of ADH22, ADH31, and ALDH21 alleles (0.91, 0.99, and 0.95, respectively) were significantly higher among the Atayal than among a predominantly Han Chinese population from Taiwan. Among the Atayal, the group with alcohol use disorders (alcohol dependence and alcohol abuse) had a significantly lower frequency of the ADH22 allele (0.82) than those without alcohol use disorders (0.91). The ADH22 allele encodes the beta 2 subunit; isozymes containing beta 2 subunits oxidize alcohol faster in vitro than the beta 1 beta 1 isozyme encoded by ADH21. Thus, the simplest explanation for these data is that individuals with a beta 2 isozymes have a higher rate of ethanol oxidation, which is a deterrent to alcohol abuse and dependence in some individuals. The Atayal with alcohol use disorders also had a lower frequency of ALDH2*2 than the controls; this allele is known to be responsible for the alcohol-flush reaction among Asians, and thereby deters drinking.
两个多态性乙醇脱氢酶基因座ADH2和ADH3以及多态性线粒体乙醛脱氢酶基因座ALDH2的基因变异，可能通过调节乙醇的消除速率以及乙醛的生成和消除速率，影响酒精中毒的发生风险。不同人群在这些基因座的等位基因频率存在差异。我们测定了台湾泰雅族原住民这三个基因座的基因型。泰雅族中ADH22、ADH31和ALDH21等位基因的频率（分别为0.91、0.99和0.95）显著高于台湾以汉族为主的人群。在泰雅族中，患有酒精使用障碍（酒精依赖和酒精滥用）的人群中ADH22等位基因的频率（0.82）显著低于无酒精使用障碍的人群（0.91）。ADH22等位基因编码β2亚基；含有β2亚基的同工酶在体外比ADH21编码的β1β1同工酶氧化酒精的速度更快。因此，对这些数据最简单的解释是，具有β2同工酶的个体乙醇氧化速率较高，这对一些个体的酒精滥用和依赖具有抑制作用。患有酒精使用障碍的泰雅族人群中ALDH2*2的频率也低于对照组；已知该等位基因会导致亚洲人出现酒精潮红反应，从而抑制饮酒。
