Hepatic messenger RNA contents of cytochrome P4502E1 in patients with different 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 most patients with ALD, suggesting that development of ALD may be genetically controlled. Although high transcriptional activity of the c2 gene was confirmed in studies using the Hep G2 cell, little is known about transcriptional activity in humans with the c2 gene. Therefore, messenger RNA (mRNA) contents of P4502E1 in livers of patients with different P4502E1 genotypes were measured. Hepatic mRNA contents in type B were three times higher than in type A, suggesting that transcriptional activity of the c2 gene of P4502E1 is stronger than that of the c1 gene, even in human liver. The results of the present study are compatible with those in the Hep G2 cells. 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.