Expression of cytochrome P4502E1 in human liver: Relationship between genotype and phenotype in Chinese |
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Authors: | Wen Tan Jianxiong Wu Huaijing Tang Dongxin Lin |
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Institution: | (1) Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 100021 Beijing, China;(2) Department of Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 100021 Beijing, China |
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Abstract: | 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 byRsa I in the 5′-regulatory region of theCYP2E1 may be a susceptibility factor for developing esophageal cancer and lung cancer in Chinese. The present study was to investigate
the relationship between theRsa I genotype and the expression of CYP2E1 in human livers. A total of 50 liver specimens were genotyped forCYP2E1 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 towardsp-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 theRsa I genotype and the phenotype of CYP2E1 in our samples, and the data are compatible with the assumption thatCYP2E1 c1/c1 genotype is a susceptibility factor for certain cancers in Chinese. |
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Keywords: | CYP2E1 Rsa I polymorphism p-nitrophenol liver microsomes |
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