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 identified in the 5-flanking region of the CYP2E1 gene that may alter the transcriptional activity. In our laboratory, no difference in c1 and c2 allele frequencies was observed between alcoholic patients with or without liver disease in Caucasian men, but there is reported data to the contrary for other populations. To determine if there is a differential susceptibility to ALD between ethnic groups that differ in the frequency of the c2 allele, we studied 30 Han Chinese with severe alcoholic liver disease. Allele frequencies of alcoholics with cirrhosis were compared with 46 alcoholic and 100 nonalcoholic Han individuals without liver disease. To identify the type A (homozygous for c1), type B (heterozygous for c1 and c2) and type C (homozygous for c2) genotypes, DNA encompassing the polymorphisms was amplified by polymerase chain reaction, 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 difference in c2 allele frequencies between alcoholic and nonalcoholic Atayal natives from Taiwan. Therefore, our results suggest that the allelic variations at the CYP2E1 gene locus also do not significantly affect the development of alcoholism or ALD in Han Chinese and Atayal natives of Taiwan.