Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Egypt.
Biochemistry Department, National Liver Institute (NLI), Menoufiya University, Sadat City, Egypt.
Immunol Invest. 2022 Apr;51(3):688-704. doi: 10.1080/08820139.2020.1869251. Epub 2021 Jan 14.
Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been demonstrated that polymorphisms in some genes may significantly predict HCV infected patients' susceptibility to developing liver cirrhosis or their responsiveness to the treatment.
We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs).
IFN-γ (+874T/A, +2109A/G) and IP-10 (-135G/A, -1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods.
IFN-γ + 874 TA, IP-10 - 135AA, and IP-10 - 1447AA and IP-10 - 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci -135 and -1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D' = 0.999, r = 0.689).
Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection.
目前有越来越多的证据表明，促炎细胞因子中个体遗传多态性与慢性丙型肝炎（CHC）的严重程度之间存在关联。已经证明，一些基因的多态性可能显著预测 HCV 感染患者发生肝硬化的易感性或对治疗的反应性。
我们研究了干扰素（IFN-γ）和干扰素诱导蛋白 10（IP-10）基因中的单核苷酸多态性（SNP）对 HCV 感染患者发生肝硬化的风险的影响，以及它们与各种直接作用抗病毒药物（DAAs）反应的关系。
采用单链构象多态性聚合酶链反应（SSP-PCR）或限制性片段长度多态性聚合酶链反应（RFLP-PCR）方法，检测 175 例埃及 HCV 慢性丙型肝炎患者（69 例肝硬化和 106 例非肝硬化患者）IFN-γ（+874T/A、+2109A/G）和 IP-10（-135G/A、-1447A/G）基因型。
与非肝硬化患者相比，发生肝硬化的患者中 IFN-γ+874TA、IP-10-135AA、IP-10-1447AA 和 IP-10-1447GG 基因型增加。尽管在它们的分布中没有显示出统计学意义，表明这些 SNP 与 HCV 感染患者发生肝硬化的易感性之间没有关联。对所有选定基因的不同基因座之间的单倍型分析显示，在肝硬化患者中，AGGA 和 TAGA 增加，TGGA 单倍型减少。IP-10 基因座-135 和-1447 处的基因型频率似乎处于完全连锁不平衡状态（D'=0.999，r=0.689）。
我们的数据支持这样的概念，即 IFN-γ 和 IP-10 基因多态性不是埃及 HCV 感染患者疾病进展的预测因子。
