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Interaction effects among IFN-{gamma}+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

BMJ Open Sep 01, 2017

Gao QJ, et al. – Researchers realized considerable variation in the natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections among individuals. To understand the mechanism, they evaluated the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. Findings suggested that 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.

Methods

  • Researchers analyzed 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.
  • Using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR, they analyzed 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/-589C>T of IL-4).
  • Assessment of the gene–gene interactions was performed using the multifactor-dimensionality reduction method.

Results

  • In this study, interleukin (IL)-10-592 AC and IL-4-589 CC/CT indicated a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874 AA and IL-2-330 TT indicated a synergistic impact (p<0.05). An antagonistic effect (p<0.01) of IFN-γ+874 AA and IL-10-1082 AA was realized on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis.
  • IL-2-330 TT and IL-10-1082 AA seemed synergistically influencing the clinical outcome (p<0.05).
  • The clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis seemed affected by IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively (p<0.05).

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