HEPATIC MESSENGER-RNA CONTENTS OF CYTOCHROME-P4502E1 IN PATIENTS WITH DIFFERENT CYTOCHROME-P4502E1 GENOTYPES

Since heavy drinkers do not always develop alcoholic liver disease (ALD), genetic factors may be involved. Cytochrome P4502E1 (P4502E1) is the main enzyme that oxidizes ethanol in the non-alcohol dehydrogenase pathway. Recently, the presence of genetic polymorphisms at the 5'-flanking region of this enzyme was confirmed. We recently detected the c2 gene of P4502E1 in all patients with ALD, suggesting that development of ALD may be genetically controlled. High transcriptional activity of the c2 gene was confirmed in studies using the Hep G2 cell by Hayashi et al. (J Biochem 1991;110:559-565), suggesting that polymorphisms of P4502E1 may be linked to the development of ALD through enhancement of ethanol metabolism in the non-alcohol dehydrogenase pathway. However, little is known about transcriptional activity in human beings with the c2 gene. Therefore, messenger RNA (mRNA) contents of P4502E1 in hepatic biopsy specimens from patients with different P4502E1 genotypes were measured. Type A of P4502E1 was not found in any patients with ALD, suggesting that development of ALD is controlled genetically and that the genotype of P4502E1 is one of the most important determining factors for its development. Hepatic mRNA contents in type B were 3-times higher than in type A, suggesting that transcriptional activity of the c2 gene of P4502E1 is stronger than that of the cl gene even in human liver. The results of the present study are quite compatible with those by Hayashi et al. using the Hep G2 cell. These results suggest that polymorphisms of the P4502E1 gene may be linked to the development of ALD through enhancement of ethanol metabolism in the non-alcohol dehydrogenase pathway.