DOI QR코드

DOI QR Code

Lack of Association between Tumor Necrosis Factor-α -308 and -238 Promoter Polymorphisms and Chronic Hepatitis B Virus Infection

종양괴사인자-α -308과 -238 promoter 다형성과 만성 B형 간염 바이러스 감염 간의 연관성 결여

  • Jang, Won-Hee (Department of Biochemistry, College of Medicine, Inje University, Paik Institute for Clinical Research, Inje University) ;
  • Yang, Young-Il (Paik Institute for Clinical Research, Inje University,Department of Pathology, College of Medicine, Inje University) ;
  • Lee, Youn-Jae (Department of Internal Medicine, College of Medicine, Inje University) ;
  • Chun, Jin-Ho (Department of Preventive Medicine, College of Medicine, Inje University) ;
  • Yea, Sung-Su (Department of Biochemistry, College of Medicine, Inje University) ;
  • Seog, Dae-Hyun (Department of Biochemistry, College of Medicine, Inje University) ;
  • Kim, Hyeong-In (Paik Institute for Clinical Research, Inje University)
  • 장원희 (인제대학교 의과대학 생화학교실, 인제대학교 의과대학 백인제기념임상의학연구소) ;
  • 양영일 (인제대학교 의과대학 백인제기념임상의학연구소, 인제대학교 의과대학 병리학교실) ;
  • 이연재 (인제대학교 의과대학 내과학교실) ;
  • 전진호 (인제대학교 의과대학 예방의학교실) ;
  • 예성수 (인제대학교 의과대학 생화학교실) ;
  • 석대현 (인제대학교 의과대학 생화학교실) ;
  • 김형인 (인제대학교 의과대학 백인제기념임상의학연구소)
  • Published : 2008.09.30

Abstract

The pro-inflammatory cytokine tumor necrosis factor-$\alpha$ (TNF-$\alpha$) is an important mediator of the immune response in hepatitis B virus (HBV) infection. Since the production of TNF-$\alpha$ is mostly regulated at the transcriptional level and polymorphisms in the TNF-$\alpha$ promoter alter its expression, TNF-$\alpha$ promoter polymorphisms could affect the pathogenesis of chronic HBV infection. In this study, we investigated the potential association of TNF-$\alpha$ promoter polymorphisms with chronic HBV infection. The study included 181 patients with chronic HBV infection, 201 persons who had been spontaneously recovered from hepatitis B, and 170 unrelated healthy controls. The -308G/A and -238G/A polymorphisms in the TNF-$\alpha$ promoter were analyzed by PCR-restriction fragment length polymorphism. The distribution of both the -308 and -238 genotypes in the patient group was not statistically different from that in the spontaneous recovery and control groups (p>0.05). There was also no significant difference in the allele frequency between the groups (p>0.05). The results suggest that the TNF-$\alpha$ -308 and -238 promoter polymorphisms are not associated with the development of chronic HBV infection in the Korean population.

Pro-inflammatory cytokine인 종양괴사인자-$\alpha$ (TNF-$\alpha$)는 B형 간염바이러스(HBV) 감염에 대한 면역반응의 중요한 매개인자이다. TNF-$\alpha$의 생산은 전사수준에서 주로 조절되며, TNF-$\alpha$ promoter 다형성은 TNF-$\alpha$ 유전자 발현을 변화시키기 때문에, TNF-$\alpha$ promoter 다형성이 만성 HBV 감염의 병태생리에 영향을 미칠 가능성이 높다. 그러므로, 본 연구에서는 TNF-$\alpha$ promoter 다형성과 만성 HBV 감염의 연관성을 조사하였다. 본 연구는 만성 HBV 감염환자 181명, HBV 감염이 자연적으로 치유된 201명, 그리고 건강한 대조군 170명을 대상으로 하였다. TNF-$\alpha$ promoter의 -308G/A와 -238G/A 다형성은 PCR-RFLP법을 통하여 분석하였다. 분석결과, 환자군에서 -308과 -238 유전자형의 분포는 자연치유군 및 건강대조군에서의 분포와 통계적인 차이를 보이지 않았다(p>0.05). 또한, 그룹 간에 allele frequency도 통계적 차이가 없었다(p>0.05). 따라서, 본 연구의 결과는 한국인에서 TNF-$\alpha$ -308과 -238 promoter 다형성은 만성 B형 간염 바이러스 감염의 발생과 연관성이 없음을 시사한다.

Keywords

References

  1. Beasley, R. P. 1988. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61, 1942-1956. https://doi.org/10.1002/1097-0142(19880515)61:10<1942::AID-CNCR2820611003>3.0.CO;2-J
  2. Ben-Ari, Z., E. Mor, O. Papo, B. Kfir, J. Sulkes, A. R. Tambur, R. Tur-Kaspa and T. Klein. 2003. Cytokine gene polymorphisms in patients infected with hepatitis B virus. Am. J. Gastroenterol. 98, 144-150. https://doi.org/10.1111/j.1572-0241.2003.07179.x
  3. Beutler, B. and A. Cerami. 1989. The biology of cachectin/TNF - a primary mediator of the host response. Annu. Rev. lmmunol. 7, 625-655. https://doi.org/10.1146/annurev.iy.07.040189.003205
  4. Cabrera, M., M. A. Shaw, C. Sharples, H. Williams, M. Castes, J. Convit and J. M. Blackwell. 1995. Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis. J. Exp. Med. 182, 1259-1264. https://doi.org/10.1084/jem.182.5.1259
  5. Cheong, J. Y., S. W. Cho, I. L. Hwang, S. K. Yoon, J. H. Lee, C. S. Park, J. E. Lee, K. B. Hahm and J. H. Kim. 2006. Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-alpha gene promoter polymorphisms. J. Gastroenterol. Hepatol. 21, 1163-1169. https://doi.org/10.1111/j.1440-1746.2006.04304.x
  6. Chisari, F. V. and C. Ferrari. 1995. Hepatitis B virus immunopathogenesis. Annu. Rev. lmmunol. 13, 29-60. https://doi.org/10.1146/annurev.iy.13.040195.000333
  7. Chouchane, L., S. B. Ahmed, S. Baccouche and S. Remadi. 1997. Polymorphism in the tumor necrosis factor-alpha promoter region and in the heat shock protein 70 genes associated with malignant tumors. Cancer 80, 1489-1496. https://doi.org/10.1002/(SICI)1097-0142(19971015)80:8<1489::AID-CNCR17>3.0.CO;2-1
  8. DAlfonso, S. and P. M. Richiardi. 1994. A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics 39, 150-154.
  9. Du, T., X. H. Guo, X. L. Zhu, J. H. Li. L. P. Lu, J. R. Gao, C. Y. Gou, Z. Li, Y. Liu and H. Li. 2006. Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population. J. Viral. Hepat. 13, 618-624. https://doi.org/10.1111/j.1365-2893.2006.00731.x
  10. Gilles, P. N., G. Fey and F. V. Chisari. 1992. Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. J. Virol. 66, 3955-3960.
  11. Gonzalez-Amaro, R., C. Garcia-Monzon, L. Garcia-Buey, R Moreno-Otero, J. L. Alonso, E. Yague, J. P. Pivel, M. Lopez-Cabrera, E. Fernandez-Ruiz and F. Sanchez-Madrid. 1994. Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis. J. Exp. Med. 179, 841-848. https://doi.org/10.1084/jem.179.3.841
  12. Guidotti, L. G., T. Ishikawa, M. V. Hobbs, B. Matzke, R Schreiber and F. V. Chisari. 1996. IntraceIlular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. lmmunity 4, 25-36.
  13. Higuchi, T., N. Seki, S. Kamizono, A. Yamada, A. Kimura, H. Kato and K. Itoh. 1998. Polymorphism of the 5-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese. Tissue Antigens 51, 605-612. https://doi.org/10.1111/j.1399-0039.1998.tb03002.x
  14. Hill, A. V. S. 1998. The immunogenetics of human infectious diseases. Annu. Rev. lmmunol. 16, 593-617. https://doi.org/10.1146/annurev.immunol.16.1.593
  15. Hohler, T., A. Kruger, G. Gerken, P. M. Schneider, K. H. Meyer zum Buschenefelde and C. Rittner. 1998. A tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated with chronic hepatitis B infection. Clin. Exp. lmmunol, 111, 579-582. https://doi.org/10.1046/j.1365-2249.1998.00534.x
  16. Hohler, T., A. Kruger, G. Gerken, P. M. Schneider, K. H. Meyer zum Buschenefelde and C. Rittner. 1998. Tumor necrosis factor alpha promoter polymorphism at position -238 is associated with chronic active hepatitis C infection. J. Med. Virol. 54, 173-177. https://doi.org/10.1002/(SICI)1096-9071(199803)54:3<173::AID-JMV5>3.0.CO;2-2
  17. Hunt, C. M., J. M. McGill, M. I. AIlen and L. D. Condreay. 2000. Clinical relevance of hepatitis B viral mutations. Hepatology 31, 1037-1044. https://doi.org/10.1053/he.2000.6709
  18. Jang, W. H, Y. I. Yang, S. S. Yea, Y. J. Lee, J. H. Chun, H. I. Kim, M. S. Kim and K. H. Paik. 2001. The -238 tumor necrosis factor-alpha promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett. 166, 41-46. https://doi.org/10.1016/S0304-3835(01)00438-4
  19. Jin, H. J., K. D. Kwak, M. F. Hammer, Y. Nakahori, T. Shinka, J. W. Lee, F. Jin, X. Jia, C. Tyler-Smith and W. Kim. 2003. V-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans. Hum Genet. 114, 27-35. https://doi.org/10.1007/s00439-003-1019-0
  20. Kaluza, W., E. Reuss, S. Grossmann, R. Hug, R E. Schopf, P. R. Galle PR, E. Maerker-Hermann and T. Hoehler. 2000. Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J. Invest. Dermatol. 114, 1180-1183. https://doi.org/10.1046/j.1523-1747.2000.00001.x
  21. Kim, Y. J., H. S. Lee, J. H. Yoon, C. Y. Kim, M. H. Park, L. H. Kim, B. L. Park and H. D. Shin. 2003. Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. Hum. Mol. Genet. 12, 2541-2546. https://doi.org/10.1093/hmg/ddg262
  22. Kroeger, K. M., K. S. Carville and L. J. Abraham. 1997. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol. Immunol. 34, 391-399. https://doi.org/10.1016/S0161-5890(97)00052-7
  23. Marinos, G., N. V. Naoumov, S. Rossol, F. Torre, P. Y. Wong, H. GaIlati, B. Portmann and R. Williams. 1995. Tumor necrosis factor receptors in patients with chronic hepatitis B virus infection. Gastroenterology 108, 1453-1463. https://doi.org/10.1016/0016-5085(95)90694-0
  24. McGuire, W., A. V. Hill, C. E. Allsopp, B. M. Greenwood and D. Kwiatkowski D. 1994. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 371, 508-510. https://doi.org/10.1038/371508a0
  25. Niro, G. A., R. Fontana, D. Gioffreda, M. R. Valvano, A. Lacobellis, D. Facciorusso and A. Andriulli. 2005. Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection. Liver Int. 25, 1175-1181. https://doi.org/10.1111/j.1478-3231.2005.01166.x
  26. Rehermann, B. 2000. Intrahepatic T cells in hepatitis B: viral control versus liver cell injury. J. Exp. Med. 191, 1263-1268. https://doi.org/10.1084/jem.191.8.1263
  27. Sambrook, J., E. F. Fritsh and Maniatis T. 1989. Molecular cloning. A laboratory manual 2nd eds. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, New York.
  28. Sheron, N., J. Lau, H. Daniels, J. Goka, A. Eddleston, G. J. Alexander and R. Williams. 1991. Increased production of tumour necrosis factor alpha in chronic hepatitis B virus infection. J. Hepatol. 12, 241-245. https://doi.org/10.1016/0168-8278(91)90945-8
  29. Skoog, T., F. M. van't Hooft, B. Kallin, S. Jovinge. S. Boquist, J. Nilsson, P. Eriksson and A. Hamsten. 1999. A common functional polymorphism (C ${\rightarrow}$ A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum. Mol. Genet. 8, 1443-1449. https://doi.org/10.1093/hmg/8.8.1443
  30. Somi, M. H, L. Najafi, B. N. Noori, A. H. Alizadeh, M. R. Aghah, A. Shavakhi, M. J. Ehsani, R. Aghazadeh, M. Masoodi, S. Amini, M. Baladast, M. R. Zali. 2006. Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with chronic hepatitis B. Indian J. Gastroenterol. 25, 14-15.
  31. Su, F. and R. J. Schneider. 1997. Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. Proc. Natl. Acad. Sci. USA 94, 8744-8749. https://doi.org/10.1073/pnas.94.16.8744
  32. Suneetha, P. V., S. K. Sarin, A. Goyal, G. T. Kumar, D. K. Shukla and S. Hissar. 2006. Association between vitamin D receptor, CCR5, TNF-alpha and TNF-beta gene polymorphisms and HBV infection and severity of liver disease. J. Hepatol. 44, 856-863. https://doi.org/10.1016/j.jhep.2006.01.028
  33. Thursz, M. R. 1997. Host genetic factors influencing the outcome of hepatitis. J. Viral. Hepat. 4, 215-220. https://doi.org/10.1046/j.1365-2893.1997.00052.x
  34. Volpes, R., J. J. van den Oord, R. De Vos and V. J. Desmet. 1992. Hepatic expression of type A and type B receptors for tumor necrosis factor. J. Hepatol. 14, 361-369. https://doi.org/10.1016/0168-8278(92)90184-Q
  35. Wilson, A. G., F. S. di Giovine, A. I. Blakemore and G. W. Duff. 1992. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum. Mol. Genet. 1, 353.
  36. Yoshioka, K., S. Kakumu, M. Arao, Y. Tsutsumi and M. Inoue. 1989. Tumor necrosis factor alpha production by peripheral blood mononuclear cells of patients with chronic liver disease. Hepatology 10, 769-773. https://doi.org/10.1002/hep.1840100504