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Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in chinese patients
Author(s) -
Chao YouChen,
Liou ShianRen,
Chung YingYing,
Tang HungShang,
Hsu ChungTe,
Li TingKai,
Yin ShihJiun
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840190214
Subject(s) - aldh2 , aldehyde dehydrogenase , alcoholic liver disease , alcohol dehydrogenase , acetaldehyde , allele , cirrhosis , genotype , alcoholic hepatitis , genotyping , ethanol metabolism , biology , allele frequency , alcohol , medicine , genetics , ethanol , gene , biochemistry
Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH 2, ADH3 and ALDH 2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH 2*2 and ADH 3*1 alleles, which encode high maximum velocity β 2 ‐ and γ 1 ‐ADH subunits, respectively, as well as a lower frequency of the ALDH 2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol‐related cirrhosis (n = 27), viral hepatitis‐related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH 2 alleles by using polymerase chain reaction–directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele‐specific oligonucleotide probes. We found that the frequencies of the alleles ADH 2*2 (57), ADH 3*1 (78) and ALDH 2*2 (9) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer. No significant differences in the allele frequencies of these three genes between the alcoholic cirrhotic patients and the alcohol‐dependent subjects without severe liver injury were found, although the alcoholic cirrhosis group tended to have a higher incidence of ALDH 2*1/*2 heterozygotes (5 of 27) than did the alcohol‐dependent group (6 of 50). The results confirm previous studies that the ADH 2*2, ADH 3*1 and ALDH 2*2 genes can affect predisposition to alcoholism in Chinese patients and suggest that the mutant ALDH 2*2 gene may influence susceptibility to alcoholic cirrhosis. (Hepatology 1994;19:360–366).