Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

BACKGROUND: The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood.

OBJECTIVES: To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes.

METHODS: 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes ( rs2069762/-330 G/T of IL-2 , rs2430561/+874A>T of IFN-γ, rs1800896/-1082G>A  and rs1800872/-592C>A of IL-10 and rs2243250/ -589 C>T of IL-4 ) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method.

RESULTS: Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874  AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874  AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05).

CONCLUSIONS: Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection.