Cytokine polymorphisms and genotypic susceptibility of HCV infection in ribavirin response to peg interferon.

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Abstract

Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.

利巴韦林对聚乙二醇干扰素反应中丙型肝炎病毒感染的细胞因子多态性和基因型易感性。
免疫反应在很大程度上受细胞因子的调节。调节编码区的遗传多态性被认为会影响细胞因子的表达。丙型肝炎病毒(HCV)感染中细胞因子水平异常似乎与疾病进展、病毒存活和治疗反应有关。目前的研究评估了与IL-6、IL-10、IL28B、IFN-γ、TGF-β和TNF-α相关的多态性对HCV感染的基因型易感性和利巴韦林对聚乙二醇干扰素的反应。使用液滴数字聚合酶链式反应(PCR)从200名健康个体和300名HCV感染患者的储存样本中评估与IL-6 A/G(rs2069837)、IL-10-1082 G/A(rs1800896)]、IL28B C/T(rs12979860)、IFN-γ+874 A/T(rs2430561)、TGF-β1-509 C/T(rss1800469)和TNF-α-308 G/A启动子(rs1800629)相关的基因多态性。IL28B、IFN-γ、TGF-β1和TNF-α的AG和AA基因型与HCV易感性和治疗结果显著相关。然而,IL-6和IL-10基因多态性与HCV对治疗的易感性反应之间没有关联。结果表明,IL28BCT、TGF-β1CT、TT和TNF-AG等AA基因型对细胞因子表达有影响,这与HCV感染的易感性和耐药性以及联合抗病毒治疗有关。
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