Comparison of cytokine gene polymorphisms in patients with chronic active hepatitis b infection and those in individuals developed protective immunity to hepatitis B virus

The reasons for the viral persistence of hepatitis B virus (HBV) infection are unknown, but are probably related to host immune factors. Among these, cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of interleukin (IL)-1?, IL-1ß, IL-1 receptor (IL-1R), IL-1 receptor antagonist (IL-1RN), IL-4?, IL-2, IL-4, IL-6, IL-10, IL-12, interferon (IFN)-?, transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-? genes. The study was performed with peripheral blood mononuclear cells obtained from a total of 67 subjects, 33 with chronic HBV infection, and 34 healthy individuals with protective immunity who recovered from HBV infection. Cytokine genotypes were determined using a polymerase chain reaction-based commercial kit (Invitrogen, USA). The frequency of CT genotype at position -889 of IL-1? gene promoter region (73.4% vs. 19.2%, p= 0.000044), GT genotype at position -1098 of IL-4 gene promoter region (66.7% vs. 11.5%, p= 0.001328), GA genotype at position-1082 of IL-10 gene promoter region (72.0% vs. 45.7%, p= 0.014), CT genotype at position -819 of IL-10 gene promoter region (63.5% vs. 31.3%, p= 0.023) and TA genotype at position +874 of IFN-? gene were statistically higher in the chronic HBV group than those of HBV infection recovered group. In addition, the frequency of CC genotype at position-889 of IL-1? gene promoter region (65.4% vs. 13.3%, p= 0.0003579), TT genotype at position-1098 of IL-4 gene promoter region (73.1% vs. 29.6%, p= 0.0015), GG genotype at position-1082 of IL-10 gene promoter region (22.9% vs. 3.1%, p= 0.015), and CC genotype at position-819 of IL-10 gene promoter region (59.3% vs. 31.2%, p= 0.023) were significantly higher in the chronic HBV group than those of HBV infection recovered group. In conclusion, among thirteen cytokines that were investigated in this study, polymorphisms in the promoter regions of IL-1?, IL-4, IL-10 and IFN-? were found to be associated with the prognosis of the HBV infection. Determination of these polymorphisms could be used to predict whether the individuals infected with HBV will develop a protective immunity or end up with a chronic infection