CYTOCHROME P4502E1 GENOTYPES, ALCOHOLISM, AND ALCOHOLIC CIRRHOSIS IN HAN CHINESE AND ATAYAL NATIVES OF TAIWAN

Genetic factors may play a role in the development of alcoholic liver disease (ALD). Cytochrome P4502E1 (CYP2E1) catalyzes the oxidation of ethanol, producing acetaldehyde and free radicals capable of reacting with and peroxidizing cell membranes. Polymorphisms have been identifi ed in the 5'-flanking region of the CYP2E1 gene that may alter the tra nscriptional activity. In our laboratory, no difference in c1 and c2 a llele frequencies was observed between alcoholic patients with or with out liver disease in Caucasian men, but there is reported data to the contrary for other populations. To determine if there is a differentia l susceptibility to ALD between ethnic groups that differ in the frequ ency of the c2 allele, we studied 30 Nan Chinese with severe alcoholic liver disease. Allele frequencies of alcoholics with cirrhosis were c ompared with 46 alcoholic and 100 nonalcoholic Nan individuals without liver disease. To identify the type A (homozygous for c1), type B (he terozygous for c1 and c2) and type C (homozygous for c2) genotypes, DN A encompassing the polymorphisms was amplified by polymerase chain rea ction, slot-blotted, and probed with allele-specific oligonucleotides. No significant differences in c2 allele frequencies were found: 0.23 for alcoholics with severe liver disease, 0.20 for alcoholics without liver disease, and 0.26 for the normal population. There also was no d ifference in c2 allele frequencies between alcoholic and nonalcoholic Atayal natives from Taiwan. Therefore, our results suggest that the al lelic variations at the CYP2E1 gene locus also do not significantly af fect the development of alcoholism or ALD in Nan Chinese and Atayal na tives of Taiwan.