The Association Between Genetic Polymorphisms of the Ethanol-metabolizing Enzymes and Susceptibility to Alcoholic Liver Cirrhosis

Jung, Sook Hyang; Lee, Han Chu; Yoon, Jung Hwan; Lee, Hyo Suk; Kim, Chung Yong

Abstract

BACKGROUND/AIMS
There is considerable variance in individual susceptibility to hepato-toxic effects of ethanol as evidenced by the finding that only about 10-20% of alcoholics develop alcoholic liver cirrhosis. The aims of this study were, 1) to get the data on the genetic polymorphisms of three major ethanol-metabolizing enzymes (ADH, CYP2E1, ALDH) in normal Korean adults, and to search for the specific genotypes influencing alcohol drinking behavior by the comparison of allele frequencies between healthy control group and heavy drinker group with or without liver disease, 2) to investigate the influence of the genetic polymorphisms of these enzymes on the susceptibility to alcoholic liver disease by the comparison of allele frequencies between heavy drinker group without liver disease and alcoholic liver cirrhosis group.
METHODS
Healthy control group included 53 healthy males in military service without evidence of liver disease or alcoholism. Heavy drinker group without liver cirrhosis included 29 males who had been drinking 80g or more of alcohol daily for more than ten years but did not have any clinical evidence of liver disease. Alcoholic cirrhosis group included 43 male patients who had drunk 80g or more of alcohol daily for more than ten years and had clinical evidences of overt cirrhosis. Subjects with hepatitis B surface antigen or anti-hepatitis C antibody were excluded. Genotypes of the three enzymes were determined by PCR (polymerase chain reaction) and restriction fragment length polymorphism (RFLP) with genomic DNAs extracted from peripheral leukocytes.
RESULTS
1) In healthy Korean males, allele frequency of ADH22, ADH31, CYP2E1 c2 and ALDH22 was 81%, 94%, 30% and 14%, respectively. 2) The absence of ALDH22 or CYP2E1 c2 allele were significant risk factors for being a heavy drinker (odds ratio,' 0.09, 0.42, respectively). 3) Although it was not associated with the polymorphism of each ethanol-metabolizing enzymes, the susceptibility to alcoholic liver cirrhosis was significantly associated with combined genotypes of ADH2(22) & ADH3(1+1)& CYP2E1 B or C. COMCLUSION: Genetic polymorphisms of ethanol-metabolizing enzyrnes are significantly associated with the suseptability to alcoholic liver disease as well as alcohol drinking behavior.