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

Abstract

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.

Human Papillomavirus Infection Is Associated with Decreased Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients: Taiwan Nationwide Matched Cohort Study

“…The role of HPV in interfering with hepatocarcinogenesis may be related to the involvement of a Toll-like receptor (TLR). Single-nucleotide polymorphisms in TLR genes may be key markers of an early susceptibility to various cancers, including HCC [ 35 ]. Since they initiate intracellular signaling pathways to induce antiviral mediators, they have been considered as the first line of antiviral immunity [ 36 ].…”

“…Since they initiate intracellular signaling pathways to induce antiviral mediators, they have been considered as the first line of antiviral immunity [ 36 ]. Studies have shown that TLR4 rs4986790 was significantly negatively associated with HCV infection [ 35 ]. Individuals carrying the rs1927911 heterozygous genotype had a significantly reduced risk of HCC [ 37 ].…”

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in hepatoblastoma

“…The participation of a Toll-like receptor (TLR) in HPV's ability to interfere with hepatocarcinogenesis has been hypothesized. Many types of tumors may be predisposed to a person with certain single-nucleotide polymorphisms in the TLR genes (94,95). Under a wide range of oncogenic situations, on the other side, cellular senescence is a critical tumor-suppressive mechanism that causes injured cells to undergo permanent growth arrest, preventing them from proliferating abnormally.…”

The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis

“…It is possible that there are functions relating to RNA stability and regulation, resulting in alteration of protein expression because several translated regions or a part of intron might relate to miRNA [36]. Moreover, previous in silico analysis showed that rs2149356G is able to form miRNA which targets autophagy genes [37]. Therefore, rs1927911 and rs12377632 should be under this circumstance.…”