Author: Tanaka, F.; Shiratori, Y.; Yokosuka, O.; Imazeki, F.; Tsukada, Y.; Omata, M.
Description: Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P-450IIEI. The purpose of this study was to clarify the role of polymorphism of these ethanol-metabolizing enzymes in drinking behavior and the progression of alcoholic liver disease among Japanese men. Polymorphism of the ADH2, ALDH2, and P-45IIEI genes were determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis in 189 normal Japanese men and 26 male patients with alcoholic liver disease. Drinking behavior was estimated by self-assessment according to DSM-III-R criteria. Facial flushing was reported in 91 subjects heterozygous for ALDH2*1/*2 and in two subjects homozygous for ALDH2*2/*2, but was not found in 96 subjects homozygous for ALDH2*1/*1. In contrast, polymorphism of ADH2 and P-450IIEI did not differ between flushers and nonflushers. Although the flushers only drank a small amount of alcohol (< 20 g of ethanol/day), the nonflushers were divided into a group of moderate drinkers (20 to 80 g/day; n = 54) and a group of heavy drinkers (> 80 g/day; n = 42). A high preponderance of heterozygosity for the ADH2*1/*2 genes (20/42; 60%) and a high frequency of the ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers. However, cytochrome P-45IIEI gene polymorphism was similar among the moderate and heavy drinkers. Not only a high frequency of the ALDH2*1 and ADH2*1 alleles, but also a high frequency of the P-450IIEI c2 allele was found in the patients with alcoholic liver disease. From these results, the drinking behavior of Japanese men is strongly influenced by the ALDH2*1 allele, and the level of alcohol intake is affected by the ADH2*1 allele, but not by cytochrome P-45IIEI. However, progression to alcoholic liver disease among heavy drinkers may be affected by the cytochrome P-450IIEI c2 allele.
Subject headings: Adult; Alcohol Dehydrogenase/genetics; Alcohol Drinking/genetics/physiopathology; Alcoholism/genetics/psychology; Aldehyde Dehydrogenase/genetics; Alleles; Cytochrome P-450 CYP2E1/genetics; Ethanol/pharmacokinetics; Ethnic Groups/genetics/psychology; Flushing/enzymology/genetics; Gene Expression Regulation, Enzymologic; Humans; Japan; Liver Diseases, Alcoholic/enzymology/genetics; Male; Middle Aged; Polymorphism, Genetic/genetics
Publication year: 1997
Journal or book title: Alcoholism, Clinical and Experimental Research
Volume: 21
Issue: 4
Pages: 596-601
Find the full text : https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1530-0277.1997.tb03808.x
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Type: Journal Article
Serial number: 517