J Korean Med Sci.  2001 Dec;16(6):745-750. 10.3346/jkms.2001.16.6.745.

Association Between Polymorphisms of Ethanol-Metabolizing Enzymes and Susceptibility to Alcoholic Cirrhosis in a Korean Male Population

• Lee HC
• Lee HS
• Jung SH
• Yi SY
• Jung HK
• Yoon JH
• Kim CY

• KMID: 648356
• DOI: http://doi.org/10.3346/jkms.2001.16.6.745

Abstract

Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and cytochrome P-4502E1 (CYP2E1), and then to acetate by aldehyde dehydrogenase (ALDH). Polymorphisms of these ethanol-metabolizing enzymes may be associated with inter-individual difference in alcohol metabolism and susceptibility to alcoholic liver disease. We determined genotype and allele frequencies of ALDH2, CYP2E1, ADH2, and ADH3 in male Korean patients with alcoholic cirrhosis (n=56), alcoholics without evidence of liver disease (n=52), and nondrinkers (n=64) by using PCR or PCR-directed mutagenesis followed by restriction enzyme digestion. The prevalences of heterozygous ALDH2*1/*2 plus homozygous ALDH2*2/*2 in patients with alcoholic cirrhosis (7.1%) and alcoholics without evidence of liver disease (3.8%) were significantly lower than that in nondrinkers (45.3%). The c2 allele frequencies of the CYP2E1 in alcoholic cirrhosis, alcoholics without evidence of liver disease, and nondrinkers were 0.21, 0.20, and 0.20, respectively. Allele frequencies of ADH2*2 in the three groups were 0.78, 0.74, and 0.77 and those of ADH3*1 were 0.94, 0.98, and 0.95. Therefore, we confirmed the observation that the ALDH2*2 gene protects against the development of alcoholism. However, the development of cirrhosis in Korean alcoholic patients was not associated with polymorphisms of ethanol-metabolizing enzymes.

Keyword

Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Cytochrome P-450 CYP2E1; Liver Cirrhosis, Alcoholic; Polymorphism (Genetics)

MeSH Terms

Adult
Alcohol Dehydrogenase/*genetics
Alcoholism/enzymology/genetics
Aldehyde Dehydrogenase/*genetics
Central Nervous System Depressants/pharmacokinetics
Cytochrome P-450 CYP2E1/*genetics
Ethanol/pharmacokinetics
Gene Frequency
Genetic Predisposition to Disease
Genotype
Human
Korea
Liver Cirrhosis, Alcoholic/enzymology/*genetics
Male
Middle Age
*Polymorphism (Genetics)