摘要
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.
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 eso-phageal 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.
基金
This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 39825122 and 39990570) and State Key Basic Research Program (Grant No. G1998051200).
