The associations between Toll-like receptor 4 gene polymorphisms and hepatitis C virus infection: a systematic review and meta-analysis

Background and objective: The hepatitis C virus (HCV) is able to cause a life-threatening disease relating to lethal hepatocellular carcinoma. Previous, Toll-like receptor polymorphisms were proposed as promising biomarker for HCV-related hepatocellular carcinoma and disease progression. This study aimed to summarize the association of TLR4 polymorphisms and HCV infection through meta-analysis. Methods: We applied a systematic review and meta-analysis performed by using PubMed, EMBASE and Web of Science searches. The Modified Newcastle-Ottawa scale was used for quality assessment. The odd-ratio (OR) and 95% confidence interval (CI) were calculated to assess the association. In silico analysis was applied for proposing the function as microRNA (miRNA) of non-coding polymorphism. Finally, the miRNA target was predicted and annotated to suggest the possible relationship between polymorphism and HCV infection. Results: Our meta-analysis incorporated seven studies involving rs4986791, rs4986790 and rs2149356. No association exists between rs4986791 and HCV infection. However, the heterozygous model (AG vs GG) of rs4986790 significantly associates with HCV infection (OR = 0.33, 95% CI = 0.21-0.49, P <0.0001). Moreover, the rs2149356 TG genotype also associates with HCV infection in the over-dominant model (TG vs TT+TG: OR = 0.54, 95% CI = 0.40-0.75). In silico analysis of rs2149356G allele showed that this mutation is siRNA, which targets the set of genes, especially in the autophagy pathway. Conclusion: We demonstrated that rs4986790 and rs2149356 are associated with HCV infection.