Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenases in individual variation of alcohol metabolism.
The involvement of genetic polymorphism at the alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) loci in determining blood acetaldehyde levels and the rate of ethanol elimination after ethanol intake was investigated. Sixty-eight healthy subjects ingested 0.4 g of ethanol per kg of body weight over 10 min. Blood acetaldehyde levels scarcely increased in the subjects homozygous for ALDH2*1, regardless of their ADH2 genotypes (ADH2*1/*1, ADH2*1/*2 and ADH2*2/*2). The acetaldehyde levels in the subjects with the ALDH2*1/*2 heterozygote increased to 23.4 microM on average, and no significant differences were observed between the three ADH2 genotype groups. Subjects homozygous for ALDH2*2 showed very high levels of blood acetaldehyde, and the average value was 79.3 microM. The values of Widmark's beta 60 (mg/ml/hr) and ethanol elimination rate (mg/kg/hr) showed significant differences among the three ALDH2 genotypes, and in decreasing order the values were ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2. However, no significant differences were seen among the ADH2 genotypes.
Mizoi
Y
Y
Department of Legal Medicine, Osaka Medical College, Japan.
Yamamoto
K
K
Ueno
Y
Y
Fukunaga
T
T
Harada
S
S
D000079:Acetaldehyde / Q000097:blood; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D002874:Chromosome Mapping; D000431:Ethanol / Q000493:pharmacokinetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012016:Reference Values
D007527:Isoenzymes; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde