Cytokines genes polymorphisms in chronic hepatitis C: Impact on susceptibility to infection and response to therapy

Background: Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection, the production of abnormal cytokine levels appears to contribute in the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes polymorphisms located within the coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the study was to evaluate the association of of IL28B rs12979860, TGF-beta 1-509, TNF-alpha 308, and IL-10-1082 polymorphisms with the susceptibility to hepatitis C virus genotype 4 infection and response to pegylated interferon-alpha and ribavirin therapy. Methods: IL28B, TGF-beta 1 and TNF-alpha genes polymorphisms were genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay while IL-10 gene polymorphism was detected by sequence specific primer-PCR in 220 healthy individuals and 440 hepatitis C infected patients (220 sustained virological response and 220 non-responder to combination therapy). Results: IL28 B CT and TT, TGF-beta 1 CT and IT and TNF-alpha AG and AA genotypes were significantly associated with susceptibility to hepatitis C infection and response to therapy. While no association was found between IL-10 gene polymorphism and susceptibility to HCV infection and response to treatment. Conclusions: These results suggested that inheritance of IL28B CT and TT, TGF-beta 1 CT and TT and TNF-alpha AG and AA genotypes which appear to affect the cytokine production may be associated with susceptibility to HCV infection and resistance to combined antiviral therapy. (C) 2012 Elsevier Ltd. All rights reserved.