Genetic variation in interleukin 28B and correlation with chronic hepatitis B virus infection in Saudi Arabian patients
Corresponding Author
Ahmed A. Al-Qahtani
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Correspondence
Ahmed Al-Qahtani, PhD
Department of Infection and Immunity,
Research Center, King Faisal Specialist Hospital & Research Center,
PO Box 3354 (MBC-03), Riyadh, 11211 Saudi Arabia
Tel:+ 966 11 442 4550
Fax:+ 966 11 442 4519
e-mail: [email protected]
Search for more papers by this authorMashael R. Al-Anazi
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorAyman A. Abdo
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorFaisal M. Sanai
Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorWaleed K. Al-Hamoudi
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorKhalid A. Alswat
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorHamad I. Al-Ashgar
Gastroenterology Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorNisreen Z. Khalaf
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorNisha A. Viswan
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorMohammed N. Al Ahdal
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorCorresponding Author
Ahmed A. Al-Qahtani
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Correspondence
Ahmed Al-Qahtani, PhD
Department of Infection and Immunity,
Research Center, King Faisal Specialist Hospital & Research Center,
PO Box 3354 (MBC-03), Riyadh, 11211 Saudi Arabia
Tel:+ 966 11 442 4550
Fax:+ 966 11 442 4519
e-mail: [email protected]
Search for more papers by this authorMashael R. Al-Anazi
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorAyman A. Abdo
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorFaisal M. Sanai
Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorWaleed K. Al-Hamoudi
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorKhalid A. Alswat
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorHamad I. Al-Ashgar
Gastroenterology Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Search for more papers by this authorNisreen Z. Khalaf
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorNisha A. Viswan
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorMohammed N. Al Ahdal
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorAbstract
Background & Aims
Several genome-wide association studies have shown that genetic variations in the chromosomal region containing interleukin-28B (IL28B) gene are associated with response to treatment in hepatitis C virus (HCV) infection. This study was conducted to examine the role of genetic variations in IL28B on disease progression in Saudi Arabian patients chronically infected with hepatitis B virus (HBV).
Methods
The study included 1128 subjects divided into four categories; 304 clearance subjects, 518 inactive carriers, 212 active carriers and 94 cirrhosis/HCC.
Results
Three single nucleotide polymorphisms (SNPs), rs12979860 (OR = 1.307; 95% CI 1.046–1.634, χ2 = 5.57 and P = 0.0183), rs12980275 (OR = 0.642; CI 0.517–0.798, χ2 = 16.17 and P = 0.0001) and rs8105790 (OR = 0.746; CI 0.592–0.941, χ2 = 6.12 and P = 0.0133), were found to be strongly associated with HBV clearance. The frequency of the G allele of rs12980275 and the C allele of rs8105790 were found to be more in clearance group than in patients and could contribute to protection against the disease. On the other hand, only rs12979860 showed significant difference in distribution when inactive group was compared to other groups (OR = 1.285; CI 1.030–1.603, χ2 = 4.95, P = 0.0261). No significant association was evident for any of the variants when active carriers were compared to cirrhosis/HCC patients. Haplotype analysis showed that a combination of A-T-T-G of rs12980275, rs8105790, rs8099917, and rs7248668, respectively, was associated with clearance of the virus (frequency = 67.5% and P = 0.015).
Conclusion
genetic variations in IL28B gene region may influence the clearance of HBV infection.
Supporting Information
Filename | Description |
---|---|
liv12347-sup-0001-TabS1.docxWord document, 14 KB | Table S1. Primers used to genotype and sequence IL28B SNPs. |
liv12347-sup-0002-TabS2.docxWord document, 23 KB | Table S2. Genotypic distribution for IL-28 gene polymorphisms when active (group 2) group was compared with cirrhosis+HCC (group 3). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Dienstag JL. Hepatitis B virus infection. N Engl J Med 2008; 359: 1486–500.
- 2Purcell RH. The discovery of the hepatitis viruses. Gastroenterology 1993; 104: 955–63.
- 3Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis 2010; 14: 1–21, vii.
- 4Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000–summary of a workshop. Gastroenterology 2001; 120: 1828–53.
- 5Lok AS, Mcmahon BJ. Chronic hepatitis B: update of recommendations. Hepatology 2004; 39: 857–61.
- 6Ganem D, Prince AM. Hepatitis B virus infection–natural history and clinical consequences. N Engl J Med 2004; 350: 1118–29.
- 7Hui CK, Leung N, Yuen ST, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology 2007; 46: 395–401.
- 8Tran TT. Immune tolerant hepatitis B: a clinical dilemma. Gastroenterol Hepatol (N Y) 2011; 7: 511–6.
- 9Wiersma ST, Mcmahon B, Pawlotsky JM, et al. Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus. Liver Int 2011; 31: 755–61.
- 10Chu CM, Liaw YF. Incidence and risk factors of progression to cirrhosis in inactive carriers of hepatitis B virus. Am J Gastroenterol 2009; 104: 1693–9.
- 11Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences. Antivir Ther 2010; 15(Suppl 3): 25–33.
- 12Giani G, Chiaramonte M, Pasini CV, Fagiolo U, Naccarato R. Hepatitis B surface antigenemia and HLA antigens. N Engl J Med 1979; 300: 1056.
- 13Hillis WD, Hillis A, Bias WB, Walker WG. Associations of hepatitis B surface antigenemia with HLA locus B specificities. N Engl J Med 1977; 296: 1310–4.
- 14Jagielski P, Sotnik D. HLA antigens in asymptomatic carriers of HBs antigen and in carriers of anti-HBs antibodies. Arch Immunol Ther Exp (Warsz) 1978; 26: 207–12.
- 15Hu L, Zhai X, Liu J, et al. Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development. Hepatology 2012; 55: 1426–31.
- 16Kamatani Y, Wattanapokayakit S, Ochi H, et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet 2009; 41: 591–5.
- 17Li S, Qian J, Yang Y, et al. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genet 2012; 8: e1002791.
- 18Mbarek H, Ochi H, Urabe Y, et al. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum Mol Genet 2011; 20: 3884–92.
- 19Nishida N, Sawai H, Matsuura K, et al. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PLoS ONE 2012; 7: e39175.
- 20Al-Qahtani A, Al-Ahdal M, Abdo A, et al. Toll-like receptor 3 polymorphism and its association with hepatitis B virus infection in Saudi Arabian patients. J Med Virol 2012; 84: 1353–9.
- 21Shi KQ, Cai XH, Xiao DD, et al. Tumour necrosis factor-alpha-857T allele reduces the risk of hepatitis B virus infection in an Asian population. J Viral Hepat 2012; 19: e66–72.
- 22Zheng MH, Xiao DD, Lin XF, et al. The tumour necrosis factor-alpha-238A allele increases the risk of chronic HBV infection in European populations. J Viral Hepat 2012; 19: e11–7.
- 23Zhang TC, Pan FM, Zhang LZ, et al. A meta-analysis of the relation of polymorphism at sites -1082 and -592 of the IL-10 gene promoter with susceptibility and clearance to persistent hepatitis B virus infection in the Chinese population. Infection 2011; 39: 21–7.
- 24Kelly C, Klenerman P, Barnes E. Interferon lambdas: the next cytokine storm. Gut 2011; 60: 1284–93.
- 25Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399–401.
- 26Suppiah V, Moldovan M, Ahlenstiel G, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009; 41: 1100–4.
- 27Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009; 41: 1105–9.
- 28Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010; 138: 1338–45, 45 e1-7.
- 29Donnelly RP, Dickensheets H, O'brien TR. Interferon-lambda and therapy for chronic hepatitis C virus infection. Trends Immunol 2011; 32: 443–50.
- 30Ank N, West H, Bartholdy C, et al. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 2006; 80: 4501–9.
- 31Ank N, Paludan SR. Type III IFNs: new layers of complexity in innate antiviral immunity. BioFactors 2009; 35: 82–7.
- 32Abdo AA, Karim HA, Al Fuhaid T, et al. Saudi Gastroenterology Association guidelines for the diagnosis and management of hepatocellular carcinoma: summary of recommendations. Ann Saudi Med 2006; 26: 261–5.
- 33Ni YH, Huang LM, Chang MH, et al. Two decades of universal hepatitis B vaccination in taiwan: impact and implication for future strategies. Gastroenterology 2007; 132: 1287–93.
- 34Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004; 11: 97–107.
- 35Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295: 65–73.
- 36Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010; 138: 1747–54.
- 37Wu JC, Huang YH, Chau GY, et al. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol 2009; 51: 890–7.
- 38Frodsham AJ, Hill AV. Genetics of infectious diseases. Hum Mol Genet 2004; 2: R187–94.
- 39Thursz M, Yee L, Khakoo S. Understanding the host genetics of chronic hepatitis B and C. Semin Liver Dis 2011; 31: 115–27.
- 40Clark PJ, Thompson AJ. Host genomics and HCV treatment response. J Gastroenterol Hepatol 2012; 27: 212–22.
- 41Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol 2006; 7: 131–7.
- 42Kiu H, Nicholson SE. Biology and significance of the JAK/STAT signalling pathways. Growth Factors 2012; 30: 88–106.
- 43Zhang L, Jilg N, Shao RX, et al. IL28B inhibits hepatitis C virus replication through the JAK-STAT pathway. J Hepatol 2011; 55: 289–98.
- 44Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009; 461: 798–801.
- 45Abe H, Ochi H, Maekawa T, et al. Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol 2010; 53: 439–43.
- 46Bochud PY, Bibert S, Kutalik Z, et al. IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatology 2012; 55: 384–94.
- 47Joshita S, Umemura T, Katsuyama Y, et al. Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection. Hum Immunol 2012; 73: 298–300.
- 48Eurich D, Boas-Knoop S, Bahra M, et al. Role of IL28B polymorphism in the development of hepatitis C virus-induced hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy. Transplantation 2012; 93: 644–9.
- 49Li W, Jiang Y, Jin Q, et al. Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population. Liver Int 2011; 31: 1118–26.
- 50Langhans B, Kupfer B, Braunschweiger I, et al. Interferon-lambda serum levels in hepatitis C. J Hepatol 2011; 54: 859–65.
- 51Lampertico P, Vigano M, Cheroni C, et al. IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B. Hepatology 2013; 57: 890–6.
- 52Sarrazin C, Susser S, Doehring A, et al. Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 2011; 54: 415–21.
- 53Balagopal A, Thomas DL, Thio CL. IL28B and the control of hepatitis C virus infection. Gastroenterology 2010; 139: 1865–76.
- 54Sonneveld MJ, Wong VW, Woltman AM, et al. Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Gastroenterology 2012; 142: 513–20e1.
- 55Fabris C, Falleti E, Cussigh A, et al. IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol 2011; 54: 716–22.
- 56Peng LJ, Guo JS, Zhang Z, et al. IL28B rs12979860 polymorphism does not influence outcomes of hepatitis B virus infection. Tissue Antigens 2012; 79: 302–5.
- 57Ren S, Lu J, Du X, et al. Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma. Cancer Immunol Immunother 2012; 61: 1433–9.
- 58Honda M, Sakai A, Yamashita T, et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 2010; 139: 499–509.