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Polymorphism of Alcohol‐Metabolizing Genes Affects Drinking Behavior and Alcoholic Liver Disease in Japanese Men
Author(s) -
Tanaka Furnika,
Shiratori Yasushi,
Yokosuka Osarnu,
Imazeki Furnio,
Tsukada Yoshio,
Omata Masao
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb03808.x
Subject(s) - aldh2 , aldehyde dehydrogenase , alcohol dehydrogenase , allele , alcoholic liver disease , medicine , loss of heterozygosity , alcohol , liver injury , liver disease , ethanol , biology , allele frequency , polymorphism (computer science) , genetics , gene , biochemistry , cirrhosis
Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P‐45011EI. 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‐45011EI genes was 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‐Ill‐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‐45011EI did not differ between flushers and nonflushers. Although the flushers only drank a small amount of alcohol (<20 g of ethanoVday), the nonflushers were divided into a group of moderate drinkers (20 to 80 glday; n = 54) and a group of heavy drinkers (780 g/day; n = 42). A high preponderance of heterozygosity for the ADH2*1/*2 genes (29/ 42; 69%) and a high frequency of the ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers. However, cytochrome P‐45011EI gene polymorphism was similar among the moderate and heavy drinkers. Not only a high frequency of the ALDHPl and ADH2*1 alleles, but also a high frequency of the P‐45011EI 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*l allele, and the level of alcohol intake is affected by the ADH2*1 allele, but not by cytochrome P‐45011EI. However, progression to alcoholic liver disease among heavy drinkers may be affected by the cytochrome P‐45011EI c2 allele.