Skip to main content

Advertisement

SpringerLink
Log in

Association of Toll-like Receptor 3 Polymorphisms with Chronic Hepatitis B and Hepatitis B-Related Acute-on-Chronic Liver Failure

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and is responsible for recognizing viral pathogens. It has been reported that the TLR3 C1234T polymorphism is associated with various diseases. The aim of this study was to investigate whether TLR3 polymorphisms were correlated with susceptibility to chronic HBV infection. Two polymorphisms in the TLR3 gene, A952T and C1234T, were tested by direct sequencing in 452 chronic hepatitis B (CHB) patients and 462 healthy controls. Data showed that subjects carrying 1234CT genotype and TT genotype had 1.42-fold and 2.31-fold increased risk of chronic HBV infection compared to those with CC genotype (95 % confidence interval [CI] = 1.08–1.86, p = 0.012; 95 % CI = 1.34–3.96, p = 0.002, respectively). Further analysis revealed that the prevalence of 1234CT genotype and T allele was significantly increased in CHB patients with acute-on-chronic liver failure (ACLF) than those without ACLF (odds ratio [OR] = 1.55, p = 0.030; OR = 1.43, p = 0.040, respectively). These results indicate that TLR3 C1234T polymorphism could be a risk factor for the development of chronic HBV infection, especially the CHB-related ACLF.

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. Tan, Y.J. 2011. Hepatitis B virus infection and the risk of hepatocellular carcinoma. World Journal of Gastroenterology 17: 4853–4857.

    Article  PubMed  CAS  Google Scholar 

  2. Gish, R., J.D. Jia, S. Locarnini, and F. Zoulim. 2012. Selection of chronic hepatitis B therapy with high barrier to resistance. The Lancet Infectious Diseases 12: 341–353.

    Article  PubMed  Google Scholar 

  3. Olson, J.C., and P.S. Kamath. 2012. Acute-on-chronic liver failure: What are the implications? Current Gastroenterology Reports 14: 63–66.

    Article  PubMed  Google Scholar 

  4. Lee, C.C., A.M. Avalos, and H.L. Ploegh. 2012. Accessory molecules for Toll-like receptors and their function. Nature Reviews Immunology 12: 168–179.

    PubMed  CAS  Google Scholar 

  5. Horscroft, N.J., D.C. Pryde, and H. Bright. 2012. Antiviral applications of Toll-like receptor agonists. The Journal of Antimicrobial Chemotherapy 67: 789–7801.

    Article  PubMed  CAS  Google Scholar 

  6. Hornung, V., S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, et al. 2002. Quantitative expression of Toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. Journal of Immunology 168: 4531–4537.

    CAS  Google Scholar 

  7. Schwarz, K., T. Storni, V. Manolova, A. Didierlaurent, J.C. Sirard, P. Rothlisberger, et al. 2003. Role of Toll-like receptors in costimulating cytotoxic T cell responses. European Journal of Immunology 33: 1465–1470.

    Article  PubMed  CAS  Google Scholar 

  8. Kaisho, T., and S. Akira. 2003. Regulation of dendritic cell function through Toll-like receptors. Current Molecular Medicine 3: 373–385.

    Article  PubMed  CAS  Google Scholar 

  9. Bsibsi, M., R. Ravid, D. Gveric, and J.M. van Noort. 2002. Broad expression of Toll-like receptors in the human central nervous system. Journal of Neuropathology and Experimental Neurology 61: 1013–1021.

    PubMed  CAS  Google Scholar 

  10. Zhou, Y., X. Wang, M. Liu, Q. Hu, L. Song, L. Ye, D. Zhou, and W. Ho. 2010. A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages. Immunology 131: 40–49.

    PubMed  CAS  Google Scholar 

  11. Li, N., Q. Li, Z. Qian, Y. Zhang, M. Chen, and G. Shi. 2009. Impaired TLR3/IFN-beta signaling in monocyte-derived dendritic cells from patients with acute-on-chronic hepatitis B liver failure: Relevance to the severity of liver damage. Biochemical and Biophysical Research Communications 390: 630–635.

    Article  PubMed  CAS  Google Scholar 

  12. Ueta, M., C. Sotozono, T. Inatomi, K. Kojima, K. Tashiro, et al. 2007. Toll-like receptor 3 gene polymorphisms in Japanese patients with Stevens–Johnson syndrome. The British Journal of Ophthalmology 91: 962–965.

    Article  PubMed  Google Scholar 

  13. Sironi, M., M. Biasin, R. Cagliani, D. Forni, M. De Luca, I. Saulle, et al. 2012. A common polymorphism in TLR3 confers natural resistance to HIV-1 infection. Journal of Immunology 188: 818–823.

    Article  CAS  Google Scholar 

  14. Mandal, R.K., G.P. George, and R.D. Mittal. 2012. Association of Toll-like receptor (TLR) 2, 3 and 9 genes polymorphism with prostate cancer risk in North Indian population. Molecular Biology Reports 39: 7263–7269.

    Article  PubMed  CAS  Google Scholar 

  15. Dai, J., Z. Hu, J. Dong, L. Xu, S. Pan, Y. Jiang, et al. 2012. Host immune gene polymorphisms were associated with the prognosis of non-small-cell lung cancer in Chinese. International Journal of Cancer 130: 671–676.

    Article  CAS  Google Scholar 

  16. Breckpot, K., D. Escors, F. Arce, L. Lopes, K. Karwacz, et al. 2010. HIV-1 lentiviral vector immunogenicity is mediated by Toll-like receptor 3 (TLR3) and TLR7. Journal of Virology 84: 5627–5636.

    Article  PubMed  CAS  Google Scholar 

  17. Daffis, S., M.A. Samuel, M.S. Suthar, M. Gale Jr., and M.S. Diamond. 2008. Toll-like receptor 3 has a protective role against West Nile virus infection. Journal of Virology 82: 10349–10358.

    Article  PubMed  CAS  Google Scholar 

  18. Klein Klouwenberg, P., L. Tan, W. Werkman, G.M. van Bleek, and F. Coenjaerts. 2009. The role of Toll-like receptors in regulating the immune response against respiratory syncytial virus. Critical Reviews in Immunology 29: 531–550.

    Article  PubMed  Google Scholar 

  19. Li, K., N.L. Li, D. Wei, S.R. Pfeffer, M. Fan, and L.M. Pfeffer. 2012. Activation of chemokine and inflammatory cytokine response in hepatitis C virus-infected hepatocytes depends on Toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediates. Hepatology 55: 666–6675.

    Article  PubMed  CAS  Google Scholar 

  20. Wu, J., M. Lu, Z. Meng, M. Trippler, R. Broering, A. Szczeponek, et al. 2007. Toll-like receptor-mediated control of HBV replication by nonparenchymal liver cells in mice. Hepatology 46: 1769–1778.

    Article  PubMed  CAS  Google Scholar 

  21. Wang, K., H. Liu, Y. He, T. Chen, Y. Yang, et al. 2010. Correlation of TLR1-10 expression in peripheral blood mononuclear cells with chronic hepatitis B and chronic hepatitis B-related liver failure. Human Immunology 71: 950–956.

    Article  PubMed  CAS  Google Scholar 

  22. Ranjith-Kumar, C.T., W. Miller, J. Sun, J. Xiong, J. Santos, I. Yarbrough, et al. 2007. Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and expression in cultured cells. The Journal of Biological Chemistry 282: 17696–17705.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the 12th Five-Year National Science and Technology Major Project for Infectious Diseases (no. 2012ZX10002004-005).

Conflict of Interest

No competing financial interests exist.

Author information

Authors and Affiliations

  1. Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China

    Yihui Rong

  2. Liver Failure Treatment and Research Center, Beijing 302 Hospital, 100 West Fourth Ring Road, Beijing, 100039, China

    Yihui Rong, Shaoli You, Bing Zhu, Hong Zang, Zhihong Wan, Hongling Liu, Aimin Zhang, Long Xiao & Shaojie Xin

  3. Department of Immunology, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Haihan Song

  4. Liver Diseases Center, Weihai 404 Hospital, 8 Baoquan Road, Weihai, 264200, China

    Yi Zhao

  5. Center for Clinic Laboratory Medicine, Beijing 302 Hospital, 100 West Fourth Ring Road, Beijing, 100039, China

    Yongli Li

Authors
  1. Yihui Rong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haihan Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaoli You
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bing Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hong Zang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongli Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhihong Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hongling Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Aimin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Long Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shaojie Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaojie Xin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rong, Y., Song, H., You, S. et al. Association of Toll-like Receptor 3 Polymorphisms with Chronic Hepatitis B and Hepatitis B-Related Acute-on-Chronic Liver Failure. Inflammation 36, 413–418 (2013). https://doi.org/10.1007/s10753-012-9560-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-012-9560-4

KEY WORDS

Search

Navigation