Yamamoto K, Ueno Y, Mizoi Y, Tatsuno Y
Department of Legal Medicine, Kobe University School of Medicine, Japan.
Arukoru Kenkyuto Yakubutsu Ison. 1993 Feb;28(1):13-25.
Influence of genetic polymorphism at the alcohol dehydrogenase2 (ADH2) and aldehyde dehydrogenase2 (ALDH2) loci on ethanol elimination and blood acetaldehyde level was studied in healthy subjects. Polymorphic regions of the ADH2 and ALDH2 genes were amplified for genomic DNA by using the technique of polymerase chain reaction. The ADH2 genotype was determined by digestion with the restriction enzyme MaeIII and the ALDH2 genotype was defined by hybridization with sequence specific oligonucleotide probes. Both loci were typed for unrelated 58 individuals by using the above methods. The gene frequencies of each locus were estimated as follows; 0.31 and 0.69 for ADH21 and ADH22, respectively, and 0.73 and 0.27 for ALDH21 and ALDH22, respectively. These values were consistent with the Hardy-Weinberg equilibrium. Pedigree analysis of 6 families with 46 subjects on both loci confirmed Mendelian inheritance. In order to investigate differences in ethanol elimination among ADH2 and ALDH2 genotype groups, 0.4 g/kg body weight of ethanol was administered to 93 subjects whose genotypes of both loci were determined by the above methods and blood ethanol and acetaldehyde levels were measured. None of the subjects homozygous for the ALDH21 allele showed facial flushing and any increase in blood acetaldehyde level. All the homozygotes and heterozygotes with the ALDH22 allele exhibited facial flushing, and the former showed a marked increase in blood acetaldehyde level and the latter did a mild increase. On the other hand, the influence of the ADH2 genotype on blood acetaldehyde level was not significant. The values of Widmark's beta 60 (mg/ml/hr) and ethanol elimination rate (mg/kg/hr) showed significant differences among the three groups of the ALDH2 genotypes in each group of the three ADH2 genotypes, and in decreasing order of both the values were ALDH 2*1/1, ALDH21/2, ALDH2/*2, However, there were no significant differences in the values among the ADH2 genotypes.
在健康受试者中研究了乙醇脱氢酶2（ADH2）和乙醛脱氢酶2（ALDH2）基因座的基因多态性对乙醇消除及血液乙醛水平的影响。采用聚合酶链反应技术对基因组DNA中ADH2和ALDH2基因的多态性区域进行扩增。通过用限制性内切酶MaeIII消化来确定ADH2基因型，通过与序列特异性寡核苷酸探针杂交来确定ALDH2基因型。使用上述方法对58名无亲缘关系的个体进行了两个基因座的分型。每个基因座的基因频率估计如下：ADH21为0.31，ADH22为0.69；ALDH21为0.73，ALDH22为0.27。这些值符合哈迪-温伯格平衡。对6个家庭中46名受试者的两个基因座进行系谱分析，证实了孟德尔遗传。为了研究ADH2和ALDH2基因型组之间乙醇消除的差异，对93名通过上述方法确定了两个基因座基因型的受试者给予0.4 g/kg体重的乙醇，并测量血液乙醇和乙醛水平。ALDH21等位基因纯合的受试者均未出现面部潮红和血液乙醛水平的任何升高。所有携带ALDH22等位基因的纯合子和杂合子均出现面部潮红，前者血液乙醛水平显著升高，后者轻度升高。另一方面，ADH2基因型对血液乙醛水平的影响不显著。在三种ADH2基因型的每组中，Widmark'sβ60（mg/ml/hr）值和乙醇消除率（mg/kg/hr）在ALDH2基因型三组之间存在显著差异，按这两个值的降序排列为ALDH 2*1/1、ALDH21/2、ALDH2/*2，然而，ADH2基因型之间这些值没有显著差异。
