The Associations between Toll-Like Receptor 4 Gene Polymorphisms and Hepatitis C Virus Infection: A systematic 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 micro-RNA (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 7 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 this mutation was siRNA, which targets the sets of genes, especially in the autophagy pathway.

CONCLUSION: We demonstrated that rs4986790 and rs2149356 are associated with HCV infection.