Skip to main content
SpringerLink
Log in

Expression of cytochrome P4502E1 in human liver: Relationship between genotype and phenotype in Chinese

  • Published:
Science in China Series C: Life Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Guengerich, F. P., Kim, D. H., Iwasaki, M., Role of human cytochrome P-450IIE1 in the oxidation of many low molecular weight cancer suspects, Chem. Res. Toxicol., 1991, 4: 168.

    Article  PubMed  CAS  Google Scholar 

  2. Albano, E., Tomasi, A., Person, J. O. et al., Role of ethanol-inducible cytochrome P-450 (CYPIIE1) in catalysing the free radical activation of aliphatic alcohols, Biochem. Pharmacol., 1991, 41: 1895.

    Article  PubMed  CAS  Google Scholar 

  3. Lechevrel, M., Casson, A. G., Wolf, C. R. et al., Characterization of cytochrome P450 expression in human oesophageal mucosa, Carcinogenesis, 1999, 20: 243.

    Article  PubMed  CAS  Google Scholar 

  4. Wheeler, C. W., Wrighton, S. A., Guenthner, T. M., Detection of human lung cytochrome P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450IIIA, Biochem. Pharmacol., 1992, 44: 183.

    Article  PubMed  CAS  Google Scholar 

  5. Lucas, D., Berthou, F., Dreano, Y. et al., Comparison of levels of cytochrome P-450, CYP1A2, CYP2E1, and their related monooxygenase activities in human surgical liver samples, Alcohol Clin. Exp. Res., 1993, 17: 900.

    Article  PubMed  CAS  Google Scholar 

  6. Lucas, D., Menez, C., Girre, C. et al., Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in health and alcoholic Caucasian subjects, Pharmacogenetics, 1995, 5: 298.

    Article  PubMed  CAS  Google Scholar 

  7. Hayashi, S., Watanabe, J., Kawajiri, K., Genetic polymorphism in the 5′-flanking region change the transcriptional regulation of the human cytochrome P450IIE1 gene, J. Biochem., 1991, 110: 559.

    PubMed  CAS  Google Scholar 

  8. Tan, W., Song, N., Wang, G. Q. et al., Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China, Cancer Epidemiol. Biomarkers Prev., 2000, 9: 551.

    PubMed  CAS  Google Scholar 

  9. Li, Z. S., Tan, W., Shao, K. et al., Susceptibility to lung cancer in Chinese is associated with polymorphism in cytochrome P4502E1, Chin. J. Oncol., 2000, 22: 5.

    Google Scholar 

  10. Tassaneeyakul, W., Veronese, M. E., Birkett, D. J. et al., High-performance liquid chromatographic assay for 4-nitrophenol hydroxylation, a putative cytochrome P-4502E1 activity, in human liver microsomes, J. Chromatogr., 1993, 616: 73.

    Article  PubMed  CAS  Google Scholar 

  11. Kim, R. B., O’shea, D., Wilkinson, G. R., Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms, Clin. Pharmacol. Ther., 1995, 57: 645.

    Article  PubMed  CAS  Google Scholar 

  12. Carriere, V., Berthou, F., Baird, S. et al., Human cytochrome P450 2E1 (CYP2E1): from genotype to phenotype, Pharmacogenetics, 1996, 6: 203.

    Article  PubMed  CAS  Google Scholar 

  13. Powell, H., Kitteringham, N. R., Pirmohamed, M. et al., Expression of cytochrome P4502E1 in human liver: assessment by mRNA, genotype and phenotype, Pharmacogenetics, 1998, 8: 411.

    Article  PubMed  CAS  Google Scholar 

  14. Le Marchand, L., Wilkinson, G. R., Wilkens, L. R., Genetic and dietary predictors of CYP2E1 activity: a phenotyping study in Hawaii Japanese using chlorzoxazone, Cancer Epidemiol. Biomarkers Prev., 1999, 8: 495.

    PubMed  CAS  Google Scholar 

  15. Perrot, N., Nalpas, B., Yang, C. S. et al., Modulation of cytochrome P450 isozymes in human liver by ethanol and drug intake, Eur. J. Clin. Invest., 1989, 19: 549.

    Article  PubMed  CAS  Google Scholar 

  16. Takahashi, T., Lasker, J. M., Rosman, A. S. et al., Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA, Hepatology, 1993, 17: 236.

    PubMed  CAS  Google Scholar 

  17. George, J., Murray, M., Byth, K. et al., Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease, Hepatology, 1995, 21: 120.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 100021, Beijing, China

    Wen Tan, Huaijing Tang & Dongxin Lin

  2. Department of Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 100021, Beijing, China

    Jianxiong Wu

Authors
  1. Wen Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianxiong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huaijing Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongxin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dongxin Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, W., Wu, J., Tang, H. et al. Expression of cytochrome P4502E1 in human liver: Relationship between genotype and phenotype in Chinese. Sci. China Ser. C.-Life Sci. 44, 356–364 (2001). https://doi.org/10.1007/BF02879602

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02879602

Keywords

Search

Navigation