Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

Vitamin D receptor gene polymorphisms and distinct clinical phenotypes of hepatitis B carriers in Taiwan

Genes & Immunity volume 11, pages 87–93 (2010)Cite this article

Abstract

Vitamin D exhibits immunomodulatory and antiproliferative effects through vitamin D receptor (VDR) in chronic infections and cancers. We genotyped the BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) polymorphisms of VDR gene in 250 Taiwanese chronic hepatitis B virus (HBV) carriers who were categorized into six phenotypes. After adjustment for age and sex, the frequencies of the VDR B/b, B/a, B/T, B/a/T in patients with hepatitis flare(s) were lower than those without (7 vs 20%, P=0.009; 1 vs 9%, P=0.004; 3 vs 10%, P=0.007; 1 vs 9%, P=0.005, respectively); in contrast, T/t, A/T, A/t, b/A/t were higher in flare(s) (8 vs 3%, P=0.003; 49 vs 34%, P=0.027; 2 vs 1%, P=0.004; 0.5 vs 0%, P=0.001, respectively). In addition, B/b, B/B, T/t, b/A, B/a, B/A, B/T, B/t, A/t, b/A/T, B/a/T, B/A/T, B/A/t, b/A/t were higher in patients positive for HBeAg. The distribution of VDR genotypes was comparable between patients with and without hepatocellular carcinoma (HCC). VDR gene polymorphisms are associated with distinct clinical phenotypes in Taiwanese HBV carriers but not with HCC development.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Lee W . Hepatitis B virus infection. N Engl J Med 1997; 337: 1733–1745.

    Article  CAS  Google Scholar 

  2. Kao JH, Chen DS . Overview of hepatitis B and C viruses. In: Goedert JJ (ed). Infectious Causes of Cancer: Targets for Intervention. Humana Press Inc.: Totowa, 2000: 313–330.

    Chapter  Google Scholar 

  3. Wasley A, Miller JT, Finelli L, CDC. Surveillance for acute viral hepatitis—United States, 2005. MMWR. Surveillance Summaries 2007; 56: 1–24.

    Google Scholar 

  4. McQuillan GM, Townsend TR, Fields HA, Carrol M, Leahy M, Polk BF . Seroepidemiology of hepatitis B virus infection in the United States. Am J Med 1989; 87 (suppl 3A): 5S–10S.

    Article  CAS  Google Scholar 

  5. CDC. Hepatitis B virus: a comprehensive strategy for limiting transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991; 40: RR-13:1–RR-13:25.

    Google Scholar 

  6. Hann HW, Hann RS, Maddrey WC . Hepatitis B virus infection in 6130 unvaccinated Korean-Americans surveyed between 1988 and 1990. Am J Gastroenterol 2007; 102: 767–772.

    Article  Google Scholar 

  7. Chen DS . From hepatitis to hepatoma: lessons from type B viral hepatitis. Science 1993; 262: 369–370.

    Article  CAS  Google Scholar 

  8. Lin KW, Kirchner JT . Hepatitis B. Am Fam Physician 2004; 69: 75–82.

    PubMed  Google Scholar 

  9. Chisari FV . Cytotoxic T cells and viral hepatitis. J Clin Invest 1997; 99: 1472–1477.

    Article  CAS  Google Scholar 

  10. Stevens CE, Beasley RP, Tsui J, Lee WC . Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975; 292: 771–774.

    Article  CAS  Google Scholar 

  11. Huo T, Wu JC, Hwang SJ, Lai CR, Lee PC, Tsay SH et al. Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study. Eur J Gastroenterol Hepatol 2000; 12: 687–693.

    Article  CAS  Google Scholar 

  12. Realdi G, Fattovich G, Hadziyannis S, Schalm SW, Almasio P, Sanchez-Tapias J et al. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. J Hepatol 1994; 21: 656–666.

    Article  CAS  Google Scholar 

  13. Forzani B, Actis GC, Verme G, Amoroso A, Borelli I, Curtoni ES et al. HLA-DR antigens in HBsAg-positive chronic active liver disease with and without associated delta infection. Hepatology 1984; 4: 1107–1110.

    Article  CAS  Google Scholar 

  14. Hattum JV, Schreuder GT, Schalm SW . HLA antigens in patients with various courses after hepatitis B virus infection. Hepatology 1987; 7: 11–14.

    Article  Google Scholar 

  15. Huang YW, Hu CY, Chen CL, Liao YT, Liu CJ, Lai MY et al. Human leukocyte antigen-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus. J Med Virol 2009; 81: 588–593.

    Article  Google Scholar 

  16. Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998; 13: 325–349.

    Article  CAS  Google Scholar 

  17. Uitterlinden AG, Fang Y, van Meurs JBJ, Pols HAP, van Leeuwen JPTM . Genetics and biology of vitamin D receptor polymorphisms. Gene 2004; 338: 143–156.

    Article  CAS  Google Scholar 

  18. Veldman CM, Cantorna MT, DeLuca HF . Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys 2000; 374: 334–338.

    Article  CAS  Google Scholar 

  19. Bellamy R, Ruwende C, Corrah T, McAdam KPWJ, Thursz M, Whittle HC et al. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis 1999; 179: 721–724.

    Article  CAS  Google Scholar 

  20. Pourgholami MH, Akhter J, Ku Y, Morris DL . In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Lett 2000; 151: 97–102.

    Article  CAS  Google Scholar 

  21. Kao JH, Chen PJ, Lai MY, Chen DS . Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol 2002; 40: 1207–1209.

    Article  Google Scholar 

  22. Bruix J, Sherman M . Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208–1236.

    Article  Google Scholar 

  23. Kao JH, Chen PJ, Lai MY, Chen DS . Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus. Hepatology 2001; 34: 817–823.

    Article  CAS  Google Scholar 

  24. Riggs BL, Nguyen TV, Melton III LJ, Morrison NA, O’Fallon WM, Kelly PJ et al. The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J Bone Miner Res 1995; 10: 991–996.

    Article  CAS  Google Scholar 

  25. Yeh SH, Tsai CY, Kao JH, Liu CJ, Kuo TJ, Lin MW et al. Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis. J Hepatol 2004; 41: 659–666.

    Article  CAS  Google Scholar 

  26. Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.

    Article  CAS  Google Scholar 

  27. Chu CM . Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2000; 15 (Suppl): E25–E30.

    Article  Google Scholar 

  28. Chu CM, Liaw YF . HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up. Hepatology 2007; 45: 1187–1192.

    Article  Google Scholar 

  29. Chu CM, Liaw YF . Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B. Gastroenterology 2007; 133: 1458–1465.

    Article  CAS  Google Scholar 

  30. Chu CM, Hung SJ, Lin J, Tai DI, Liaw YF . Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med 2004; 116: 829–834.

    Article  CAS  Google Scholar 

  31. Shiffman ML, Stewart CA, Hofmann CM, Contos MJ, Luketic VA, Sterling RK et al. Chronic infection with hepatitis C virus in patients with elevated or persistently normal serum alanine aminotransferase levels: comparison of hepatic histology and response to interferon therapy. J Infect Dis 2000; 182: 1595–1601.

    Article  CAS  Google Scholar 

  32. Suneetha PV, Sarin SK, Goyal A, Kumar GT, Shukla DK, Hissar S . Association between vitamin D receptor, CCR5, TNF-α and TNF-β gene polymorphisms and HBV infection and severity of liver disease. J Hepatol 2006; 44: 856–863.

    Article  CAS  Google Scholar 

  33. Li JH, Chen DM, Li Z, Liu Y, Gao JR, Zeng XJ et al. Study on association between vitamin D receptor gene polymorphisms and the outcomes of HBV infection. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2006; 23: 402–405.

    CAS  PubMed  Google Scholar 

  34. Li JH, Li HQ, Li Z, Liu Y, Gao JR, Zeng XJ et al. Association of TaqI T/C and FokI C/T polymorphisms of vitamin D receptor gene with outcome of hepatitis B virus infection. Zhonghua Yi Xue Za Zhi 2006; 86: 1952–1956.

    CAS  PubMed  Google Scholar 

  35. Lok ASF, McMahon BJ . AASLD practice guidelines. Chronic hepatitis B. Hepatology 2007; 45: 507–539.

    Article  CAS  Google Scholar 

  36. Valdivielso JM, Fernandez E . Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006; 371: 1–12.

    Article  CAS  Google Scholar 

  37. Potter DM . A permutation test for inference in logistic regression with small- and moderate-sized data sets. Stat Med 2005; 24: 693–708.

    Article  Google Scholar 

  38. Pourgholami MH, Morris DL . 1,25-dihydroxyvitamin D3 in lipiodol for the treatment of hepatocellular carcinoma: cellular, animal and clinical studies. J Steroid Biochem Mol Biol 2004; 89–90: 513–518.

    Article  Google Scholar 

  39. Dalhoff K, Dancey J, Astrup L, Skovsgaard T, Hamberg KJ, Lofts FJ et al. A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma. Br J Cancer 2003; 89: 252–257.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the National Taiwan University Hospital; Cathay General Hospital (97-CGN01), Department of Health and the National Science Council, Executive Yuan, Taiwan; National Health Research Institutes, Taiwan; and Liver Disease Prevention and Treatment Research Foundation.

Author information

Authors and Affiliations

  1. Liver Unit, Cathay General Hospital Medical Center, Taipei, Taiwan

    Y-W Huang, J-T Hu & S-S Yang

  2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan

    Y-W Huang, C-J Liu, M-Y Lai, P-J Chen, D-S Chen & J-H Kao

  3. Graduate Institute of Epidemiology, National Taiwan University College of Public Health, Taipei, Taiwan

    Y-T Liao

  4. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

    W Chen, D-S Chen & J-H Kao

  5. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    C-L Chen, C-J Liu, M-Y Lai, P-J Chen, D-S Chen & J-H Kao

  6. School of Medicine, Fu Jen Catholic University College of Medicine, Taipei, Taiwan

    J-T Hu & S-S Yang

  7. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

    M-Y Lai, P-J Chen & J-H Kao

Authors
  1. Y-W Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y-T Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C-L Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J-T Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C-J Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M-Y Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P-J Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D-S Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S-S Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J-H Kao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J-H Kao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, YW., Liao, YT., Chen, W. et al. Vitamin D receptor gene polymorphisms and distinct clinical phenotypes of hepatitis B carriers in Taiwan. Genes Immun 11, 87–93 (2010). https://doi.org/10.1038/gene.2009.65

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2009.65

Keywords

This article is cited by

Search

Advanced search

Quick links