Association of IL-28B, TBX21 gene polymorphisms and predictors of virological response for chronic hepatitis C
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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. The outcomes of both spontaneous HCV clearance and response to therapy depend on both viral and host factors. To investigate the influence of polymorphisms of IL-28B rs12979860 and TBX21 rs17250932, rs4794067 as well as viral factors (HCV genotype, F protein) on the outcome of HCV infection, we genotyped 565 patients with chronic HCV infection, 191 patients spontaneously resolved from HCV infection, 359 healthy controls and 383 treatment-naïve CHC patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV). Results showed that TBX21 rs4794067 variant genotypes significantly correlated with increased risk of HCV chronic infection (dominant model: OR = 5.690, 95% CI = 2.024-16.000) and susceptibility (dominant model: OR = 5.658, 95% CI = 2.514-12.735). We also found that the rs12979860, rs2227982 and rs36084323 polymorphisms showed no significant associations with susceptibility or spontaneous clearance of HCV in the anti-F antibody subgroup; however, the anti-F antibody positive subgroup might show an increased risk of N-SVR (all P < 0.001). Our results demonstrate that variant factors in both the host and pathogen are commonly important for HCV clearance. In addition rs4794067 and F protein status may be strong predictive markers in the Chinese population.
We would like to thank all of the participants in this study, particularly the patients.
Compliance with ethical standards
Conflict of interest
All authors declare that no conflict of interest exists regarding the work reported in this manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics committee of Nanjing Medical University and ethics approval was obtained from the Human Investigation Committee of the Huadong Research Institute for Medicine and Biotechnics (Nanjing, China).
- 2.Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association (2015) Guidelines for the prevention and treatment of chronic hepatitis C: a 2015 update. Chin J Liver Dis 23:888–905Google Scholar
- 7.Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K (2011) Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet 43:455–458CrossRefPubMedGoogle Scholar
- 9.Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798–801CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Stättermayer AF, Stauber R, Hofer H, Rutter K, Beinhardt S, Scherzer TM, Zinober K, Datz C, Maieron A, Dulic-Lakovic E, Kessler HH, Steindl-Munda P, Strasser M, Krall C, Ferenci P (2011) Impact of IL28B genotype on the early and sustained virologic response in treatment-naïve patients with chronic hepatitis C. Clin Gastroenterol Hepatol 9:344–350CrossRefPubMedGoogle Scholar
- 19.Large MK, Kittlesen DJ, Hahn YS (1999) Suppression of host immune response by thecore protein of hepatitis C virus: possible implications for hepatitis C virus persistence. J Immunol 162:2931–2938Google Scholar
- 25.Mehta M, Hetta HF, Abdel-Hameed EA, Rouster SD, Hossain M, Mekky MA, Khalil NK, Mohamed WA, El-Feky MA, Ahmed SH, Daef EA, El-Mokhtar MA, Abdelwahab SF, Medhat A, Sherman KE, Shata MT (2016) Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients. Arch Virol 161:3161–3169CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Stättermayer AF, Strassl R, Maieron A, Rutter K, Stauber R, Strasser M, Beinhardt S, Datz C, Scherzer TM, Steindl-Munda P, Gschwantler M, Trauner M, Hofer H, Ferenci P (2014) Polymorphisms of interferon-λ4 and IL28B effects on treatment response to interferon/ribavirin in patients with chronic hepatitis C. Aliment Pharmacol Ther 39:104–111CrossRefPubMedGoogle Scholar
- 31.Costantino A, Spada E, Equestre M, Bruni R, Tritarelli E, Coppola N, Sagnelli C, Sagnelli E, Ciccaglione AR (2015) Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C. Virol J 12:186CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Childs K, Merritt E, Considine A, Sanchez-Fueyo A, Agarwal K, Martinez-Llordella M, Carey I (2017) Immunological predictors of nonresponse to directly acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. Open Forum Infect Dis 3:67Google Scholar