Expression of cytochrome P4502E1 in human liver: Relationship between genotype and phenotype in Chinese.
Polymorphic cytochrome P4502E1 (CYP2E1) plays an important role in the metabolic activation of many carcinogens. We have previously shown that the c1/c1 genotype recognized by Rsa I in the 5'-regulatory region of the CYP2E1 may be a susceptibility factor for developing esophageal cancer and lung cancer in Chinese. The present study was to investigate the relationship between the Rsa I genotype and the expression of CYP2E1 in human livers. A total of 50 liver specimens were genotyped for CYP2E1 and assayed for CYP2E1 protein contents and functional activity by using specific antibody in immunoblot and a probe substrate,p-nitrophenol. A considerable interindividual variation in CYP2E1 protein (20-fold) and functional activity (56-fold) was observed among these liver samples. However, when they were categorized according to genotype, the mean content of CYP2E1 protein was significantly higher among individuals with the c1/c1 genotype than that among those having c1/c2 or c2/c2 genotype [124.0+/-83.9 pmol/mg (n = 28) versus 65.5 +/-38.9 pmol/mg (n = 22),P<0.01]. The mean activity of CYP2E1 towards p-nitrophenol for the c1/c1 genotype was also higher than that for the variant genotypes (198.4+/-27.8 pmol/min/mg versus 101.2 +/-18.1 pmol(-1) . min(-1) . mg(-1),P<0.01). Also, the protein levels and functional activity showed a significant correlation (r = 0.68,P<0.01). These results demonstrate an association between the Rsa I genotype and the phenotype of CYP2E1 in our samples, and the data are compatible with the assumption that CYP2E1 c1/c1 genotype is a susceptibility factor for certain cancers in Chinese.
Tan
W
W
Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Wu
J
J
Tang
H
H
Lin
D
D