Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to alcoholic liver cirrhosis.

Abstract

Cytochrome P450IIE1 (P450IIE1) is involved in ethanol metabolism and in the metabolic activation of carcinogenic nitrosoamines. The purpose of our investigation was to determine whether P450IIE1 restriction fragment length polymorphisms (RFLP) were associated with the development of alcoholic cirrhosis in Japanese alcoholics. We determined the human P450IIE1 RFLP with the restriction endonucleases, RsaI and PstI, using the polymerase chain reaction (PCR) on lymphocytes from 82 male Japanese alcoholics. Twenty patients had alcoholic fatty liver or nonspecific reaction (nonfibrotic group), and 62 had severe hepatic fibrosis or liver cirrhosis (fibrotic group). PCR-RFLP revealed three P450IIE1 genotypes, namely, heterozygotes [type B (c1/c2)] and two homozygotes [types A (c1/c1) and C (c2/c2)]. Homozygotes (c1/c1) were significantly more prevalent in the fibrotic group than in the nonfibrotic group (p < 0.05). This result suggests that susceptibility to alcoholic liver cirrhosis may be associated with the RsaI and PstI polymorphism of the P450IIE1 gene.