Alcohol‐Metabolizing Enzyme Polymorphisms and Alcoholism in Japan

• DOI: 10.1111/j.1530-0277.1995.tb00972.x
• Publication Date: 2006-04-11T12:01:08Z
• Authors: Yoshihiko Maezawa; Masayoshi Yamauchi; Gotaro Toda; Hitoshi Suzuki; Susumu Sakurai
• Keywords: Adult; Male; 0301 basic medicine; Polymorphism, Genetic; Ethanol; Genotype; Alcohol Dehydrogenase; Cytochrome P-450 CYP2E1; Oxidoreductases, N-Demethylating; Aldehyde Dehydrogenase; Middle Aged; Isoenzymes; Alcoholism; 03 medical and health sciences; Cytochrome P-450 Enzyme System; Gene Frequency; Japan; Liver; Ethnicity; Humans; Polymorphism, Restriction Fragment Length; Aged

The liver enzymes, alcohol dehydrogenase (ADH) and aldehyde de‐hydrogenase (ALDH), which are responsible for the oxidative metabolism of ethanol, are polymorphic in humans. Cytochrome P450IIE1, an ethanol‐inducible isozyme of liver microsomal P450, is also important in ethanol metabolism. Genetic polymorphisms in the 5′‐flanking region of the human cytochrome P450IIE1 gene have recently been reported. We hypothesized that the polymorphisms of ADH, ALDH, and P450IIE1 modify the susceptibility to development of alcoholism. We determined the genotypes of the ADH2, ALDH2, and P450IIE1 loci of 96 Japanese alcoholics and 60 healthy male subjects, using leukocyte DNA by the restriction fragment‐length polymorphism by polymerase chain reaction. The alcoholics had significantly higher frequencies of the ADH21 and ALDH21 alleles than did the healthy subjects. No significant difference in the frequency of the P45011E1 genotype was observed between the alcoholics and the healthy subjects. In conclusion, genetic polymorphisms of the ADH and ALDH genes, but not of the P45011E1 gene, influence the risk of developing alcoholism in Japanese.