Characterization of liver microsomal 7-ethoxycoumarin O-deethylation and chlorzoxazone 6-hydroxylation activities in Japanese and Caucasian subjects genotyped for CYP2E1 gene

Arch Toxicol. 2000 Sep;74(7):372-8. doi: 10.1007/s002040000151.

Abstract

To determine whether the CYP2E1 genetic polymorphisms cause alterations in protein expression and enzyme catalytic activities, three CYP2E1 genetic polymorphisms, namely RsaI/PstI, DraI, and MspI types, were determined in liver genomic DNA isolated from 39 Japanese and 45 Caucasians. These genotypes were compared with levels of CYP2E1 and activities of 7-ethoxycoumarin O-deethylation and chlorzoxazone 6-hydroxylation in liver microsomes from these human samples. In combination of three types of CYP2E1 polymorphisms, it was classified into seven genotypes in the Japanese population and four in the Caucasian population. The incidence in the occurrence of RsaI/PstI polymorphism or DraI polymorphism was 0.24 and 0.29 for Japanese, and 0.01 and 0.02 for Caucasians. Ethnic difference was also noted in the MspI polymorphism in which frequencies in Japanese and Caucasian populations were 0.15 and 0.02, respectively. Studies with liver microsomes showed that there were no significant differences in the levels of expression of CYP2E1 protein between wild-type (group A) and other 6 genotypes (B, C, D, E, F, and G) in Japanese and other three genotypes (B, D, and F) in Caucasians. Catalytic activities for 7-ethoxycoumarin O-deethylation and chlorzoxazone 6-hydroxylation by liver microsomes were also found to be less significantly affected by mutations in the CYP2E1 gene in human samples examined in this study. These results support the view that RsaI/PstI, DraI, and MspI types of CYP2E1 genetic polymorphisms may not cause significant alterations in protein expression and enzyme catalytic activities of CYP2E1 enzyme in human livers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group*
  • Chlorzoxazone / analogs & derivatives*
  • Chlorzoxazone / metabolism*
  • Chromatography, High Pressure Liquid
  • Coumarins / metabolism*
  • Cytochrome P-450 CYP2E1 / genetics*
  • DNA / analysis
  • European Continental Ancestry Group*
  • Genotype
  • Humans
  • Hydroxylation
  • Japan
  • Microsomes, Liver / metabolism*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic

Substances

  • Coumarins
  • 6-hydroxychlorzoxazone
  • 7-ethoxycoumarin
  • DNA
  • Cytochrome P-450 CYP2E1
  • Chlorzoxazone