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Rather than Rs1800796 Polymorphism, Expression of Interleukin-6 Is Associated with Disease Progression of Chronic HBV Infection in a Chinese Han Population

DOI: 10.1155/2013/508023

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Abstract:

Interleukin-6 plays an important role in chronic inflammation as well as tumor growth and progression. Here, a case-control study was undertaken to investigate the association of rs1800796 polymorphism of IL-6 gene and serum levels with disease progression of chronic HBV infection. Rs1800796 polymorphism was genotyped in 641 Chinese Han patients with chronic HBV infection, including 23 IT, 25 IC, 292 CHB, 153 LC, and 148 HCC patients and 265 healthy controls. Serum IL-6 levels were measured in 23 IT, 25 IC, 47 CHB, 41 LC, and 49 HCC patients and 45 healthy controls, and the classifications of HCC were accorded to BCLC staging system. We found no significant association between rs1800796 polymorphism and disease progression of chronic HBV infection; however, serum IL-6 levels showed significant statistical differences between patients with CHB, LC, and HCC. Moreover, statistical differences can be observed in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. Our findings suggest that rs1800796 polymorphism unlikely contribute significantly to affect the progression of chronic HBV infection, and serum IL-6 levels can act as a useful indicator for disease progression and severity of chronic HBV infection. 1. Introduction Hepatitis B virus (HBV) infection is a global public health problem. It is estimated that over 2 billion people have had contact with the HBV, and that 350–400 million people are chronically infected [1–3]. The clinical course of HBV infection varies from spontaneous recovery after acute hepatitis to a chronic persistent infection that may progress to cirrhosis or hepatocellular carcinoma (HCC). The outcomes of chronic HBV infection do not appear to be determined by the viral strains in themselves [4]. It has been established through twin studies that chronic HBV infection outcome has a strong genetic component [5]. Moreover, allelic variants in the human genome have been implicated in disease progression after HBV infection [6–8]. Thus, it is conceivable that genetic differences play an additional role in the influence of disease progression. Recently, compelling evidence has shown that inflammation has an important role in initiation, promotion, and progression of HBV infection [9, 10]. As a well-recognized inflammatory cytokine, interleukin-6 (IL-6) plays a central role in the regulation of immune response. Previous studies have found that serum level of IL6 was increased in patients with chronic hepatitis B (CHB) and HCC [11–13]. Moreover, in vitro and animal models studies have shown

References

[1]  W. M. Lee, “Hepatitis B virus infection,” The New England Journal of Medicine, vol. 337, no. 24, pp. 1733–1745, 1997.
[2]  A. S. F. Lok and B. J. McMahon, “Chronic hepatitis B,” Hepatology, vol. 34, no. 6, pp. 1225–1241, 2001.
[3]  M. J. Alter, “Epidemiology and prevention of hepatitis B,” Seminars in Liver Disease, vol. 23, no. 1, pp. 39–46, 2003.
[4]  I. Cacciola, G. Cerenzia, T. Pollicino et al., “Genomic heterogeneity of Hepatitis B Virus (HBV) and outcome of perinatal HBV infection,” Journal of Hepatology, vol. 36, no. 3, pp. 426–432, 2002.
[5]  T. M. Lin, C. J. Chen, M. M. Wu et al., “Hepatitis B virus marker in Chinese twins,” Anticancer Research, vol. 9, no. 3, pp. 737–741, 1989.
[6]  M. Thursz, “Genetic susceptibility in chronic viral hepatitis,” Antiviral Research, vol. 52, no. 2, pp. 113–116, 2001.
[7]  K. Migita, Y. Maeda, S. Abiru et al., “Polymorphisms of interleukin-1β in Japanese patients with hepatitis B virus infection,” Journal of Hepatology, vol. 46, no. 3, pp. 381–386, 2007.
[8]  G. Deng, G. Zhou, R. Zhang et al., “Regulatory polymorphisms in the promoter of CXCL10 gene and disease progression in male hepatitis B virus carriers,” Gastroenterology, vol. 134, no. 3, pp. 716.e2–726.e2, 2008.
[9]  M. Ayada, T. Ishikawa, A. Okumura et al., “Alteration of serum cytokine balances among different phases of chronic hepatitis B virus infection,” Hepatology Research, vol. 34, no. 4, pp. 214–221, 2006.
[10]  W. J. Du, J. H. Zhen, Z. Q. Zeng, et al., “Expression of Interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection,” Diagnostic Pathology, vol. 8, article 40, 2013.
[11]  L. Giannitrapani, M. Cervello, M. Soresi et al., “Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma,” Annals of the New York Academy of Sciences, vol. 963, pp. 46–52, 2002.
[12]  L. H. Song, V. Q. Binh, D. N. Duy et al., “Serum cytokine profiles associated with clinical presentation in Vietnamese infected with hepatitis B virus,” Journal of Clinical Virology, vol. 28, no. 1, pp. 93–103, 2003.
[13]  C. Porta, M. de Amici, S. Quaglini et al., “Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma,” Annals of Oncology, vol. 19, no. 2, pp. 353–358, 2008.
[14]  W. E. Naugler, T. Sakurai, S. Kim et al., “Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production,” Science, vol. 317, no. 5834, pp. 121–124, 2007.
[15]  W. E. Naugler and M. Karin, “The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer,” Trends in Molecular Medicine, vol. 14, no. 3, pp. 109–119, 2008.
[16]  D. Fishman, G. Faulds, R. Jeffey et al., “The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis,” Journal of Clinical Investigation, vol. 102, no. 7, pp. 1369–1376, 1998.
[17]  S. Bao, W. Yang, S. Zhou, and Z. Ye, “Relationship between single nucleotide polymorphisms in -174G/C and -634C/G promoter region of interleukin-6 and prostate cancer,” Journal of Huazhong University of Science and Technology, vol. 28, no. 6, pp. 693–696, 2008.
[18]  R. Gangwar, B. Mittal, and R. D. Mittal, “Association of interleukin-6 -174G>C promoter polymorphism with risk of cervical cancer,” International Journal of Biological Markers, vol. 24, no. 1, pp. 11–16, 2009.
[19]  Y. Tong, Z. Wang, Y. Geng et al., “The association of functional polymorphisms of IL-6 gene promoter with ischemic stroke: analysis in two Chinese populations,” Biochemical and Biophysical Research Communications, vol. 391, no. 1, pp. 481–485, 2010.
[20]  Y. Yu, W. Wang, S. Zhai, S. Dang, and M. Sun, “IL6 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review,” Molecular Biology Reports, vol. 39, no. 8, pp. 8457–8463, 2012.
[21]  R. Zhai, G. Liu, C. Yang, C. Huang, C. Wu, and D. C. Christiani, “The G to C polymorphism at -174 of the interleukin-6 gene is rare in a southern Chinese population,” Pharmacogenetics, vol. 11, no. 8, pp. 699–701, 2001.
[22]  B. L. Park, H.-S. Lee, Y. J. Kim et al., “Association between interleukin 6 promoter variants and chronic hepatitis B progression,” Experimental and Molecular Medicine, vol. 35, no. 2, pp. 76–82, 2003.
[23]  J. Bruix and M. Sherman, “Management of hepatocellular carcinoma,” Hepatology, vol. 42, no. 5, pp. 1208–1236, 2005.
[24]  C.-K. Hui and G. K. K. Lau, “Immune system and hepatitis B virus infection,” Journal of Clinical Virology, vol. 34, no. 1, pp. S44–S48, 2005.
[25]  C.-F. Huang, S.-S. Lin, Y.-C. Ho, F.-L. Chen, and C.-C. Yang, “The immune response induced by hepatitis B virus principal antigens,” Cellular & Molecular Immunology, vol. 3, no. 2, pp. 97–106, 2006.
[26]  D. E. Cressman, L. E. Greenbaum, R. A. DeAngelis et al., “Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice,” Science, vol. 274, no. 5291, pp. 1379–1383, 1996.
[27]  C.-Y. Hsia, T.-I. Huo, S.-Y. Chiang et al., “Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma,” European Journal of Surgical Oncology, vol. 33, no. 2, pp. 208–212, 2007.
[28]  X. Zhang, X. Hong, G. Deng, and X. Bai, “Single nucleotide polymorphisms and functional analysis of class II transactivator (CIITA) promoter IV in persistent HBV infection,” Journal of Clinical Virology, vol. 40, no. 3, pp. 197–201, 2007.
[29]  P. An, C. Winkler, L. Guan et al., “A common HLA-DPA1 variant is a major determinant of hepatitis B virus clearance in Han Chinese,” Journal of Infectious Diseases, vol. 203, no. 7, pp. 943–947, 2011.
[30]  J. F. Wu, C. H. Chen, Y. H. Ni, et al., “Toll-like receptor and hepatitis B virus clearance in chronic infected patients: a long-term prospective cohort study in Taiwan,” Journal of Infectious Diseases, vol. 206, no. 5, pp. 662–668, 2012.
[31]  W. P. Chong, Y. F. To, W. K. Ip et al., “Mannose-binding lectin in chronic hepatitis B virus infection,” Hepatology, vol. 42, no. 5, pp. 1037–1045, 2005.
[32]  C. Berasain, J. Castillo, M. J. Perugorria, M. U. Latasa, J. Prieto, and M. A. Avila, “Inflammation and liver cancer: new molecular links,” Annals of the New York Academy of Sciences, vol. 1155, pp. 206–221, 2009.
[33]  S. Kakumu, T. Shinagawa, T. Ishikawa et al., “Serum interleukin 6 levels in patients with chronic hepatitis B,” American Journal of Gastroenterology, vol. 86, no. 12, pp. 1804–1808, 1991.
[34]  A. Khoruts, L. Stahnke, C. J. McClain, G. Logan, and J. I. Allen, “Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients,” Hepatology, vol. 13, no. 2, pp. 267–276, 1991.
[35]  H. Nakagawa, S. Maeda, H. Yoshida et al., “Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences,” International Journal of Cancer, vol. 125, no. 10, pp. 2264–2269, 2009.
[36]  S. Maurizio, G. Lydia, D. Fabio et al., “Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma,” World Journal of Gastroenterology, vol. 12, no. 16, pp. 2563–2568, 2006.
[37]  J. Napoli, G. A. Bishop, and G. W. McCaughan, “Increased intrahepatic messenger RNA expression of interleukins 2, 6, and 8 in human cirrhosis,” Gastroenterology, vol. 107, no. 3, pp. 789–798, 1994.
[38]  K. Toda, N. Kumagai, K. Tsuchimoto et al., “Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis,” Journal of Gastroenterology, vol. 35, no. 3, pp. 214–220, 2000.
[39]  Y. Lee, U.-S. Park, I. Choi, S. K. Yoon, Y. M. Park, and Y. I. Lee, “Human interleukin 6 gene is activated by hepatitis B virus-X protein in human hepatoma cells,” Clinical Cancer Research, vol. 4, no. 7, pp. 1711–1717, 1998.
[40]  J. S. Reichner, J. A. Mulligan, R. Spisni, E. A. Sotomayor, J. E. Albina, and K. I. Bland, “Effect of IL-6 overexpression on the metastatic potential of rat hepatocellular carcinoma cells,” Annals of Surgical Oncology, vol. 5, no. 3, pp. 279–286, 1998.
[41]  K. Kovalovich, W. Li, R. DeAngelis, L. E. Greenbaum, G. Ciliberto, and R. Taub, “Interleukin-6 protects against Fas-mediated feath by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL,” Journal of Biological Chemistry, vol. 276, no. 28, pp. 26605–26613, 2001.

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