Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population.
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.
Lee
H C
HC
Department of Internal Medicine, Seoul National University, College of Medicine, Korea. hslee@medicine.snu.ac.kr
Lee
H S
HS
Jung
S H
SH
Yi
S Y
SY
Jung
H K
HK
Yoon
J H
JH
Kim
C Y
CY
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000493:pharmacokinetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007723:Korea; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D002492:Central Nervous System Depressants; D000431:Ethanol; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial