Background and Aims: Genetic polymorphisms of Toll-like receptors (TLRs) have been proposed to affect susceptibility to HCV infection and progression to end-stage liver disease. This study was conducted to clarify the association of SNPS of TLR2 and TLR4 with clinical outcome of hepatitis C, response to treatment and development of HCC. Methods: The current study examined 3295 individuals from 725 families that were categorized into groups comprising chronic HCV (CH), spontaneous viral clearance (SC) and control subjects. Treated patients were classified into responders (RT) and non-responders (NRT). In addition, patients with liver cirrhotic (LC), and hepatocellular carcinoma (HCC) were also included. All subjects were genotyped for five single nucleotide polymorphisms (SNPs) of TLR2 and four SNPs of TLR4 and their haplotypes using allelic discrimination real-time PCR. Results: Results demonstrated strong association with allele A of rs13105517 of TLR2 and allele C of rs10116253 of TLR4 with CH in comparison to SC group. However, The peak of risk of HCC was observed with allele C of rs3804099 of TLR2 and C allele of rs10116253 TLR4 (p < 0.001).A strong association was found with allele T of rs1816702 of TLR2 and allele A of rs5030728 of TLR4 in non responder group in comparison to responders (p < 0.001). Haplotypes CAGT of TLR4 and ATAC of TLR2 showed significant association with CH and HCC groups in comparison to other groups. Conclusions: This study shows an association of minor alleles of TLR2 and TLR4 with outcome of HCV infection, response to therapy and development of HCC in cirrhotic patients.

中文翻译：

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肝硬化HCV患者中Toll样受体2（TLR2）和TLR 4基因变异对HCV易感性，对肝细胞癌治疗和发展的反应。

背景与目的：已提出Toll样受体（TLR）的遗传多态性会影响对HCV感染的敏感性并发展为晚期肝病。进行这项研究以阐明TLR2和TLR4的SNPS与丙型肝炎的临床结局，对治疗的反应以及HCC的发展之间的关系。方法：本研究检查了来自725个家庭的3295名个体，这些个体分为慢性HCV（CH），自发病毒清除率（SC）和对照组。治疗的患者分为反应者（RT）和非反应者（NRT）。此外，还包括肝硬化（LC）和肝细胞癌（HCC）的患者。使用等位基因鉴别实时PCR对所有受试者的TLR2的五个单核苷酸多态性（SNP）和TLR4的四个SNP及其单倍型进行基因分型。结果：与SC组相比，结果显示与CHR的TLR2的rs13105517的等位基因A和TLR4的rs10116253的等位基因C密切相关。然而，在非TLR2的rs3804099等位基因C和rs10116253 TLR4的C等位基因C中观察到了HCC风险峰值（p <0.001）。应答者组与应答者相比（p <0.001）。与其他组相比，TLR4的单倍型CAGT和TLR2的ATAC显示与CH和HCC组显着相关。结论：这项研究表明TLR2和TLR4的次要等位基因与HCV感染的结局有关，