Gene Polymorphisms of <i>TLR2</i> and <i>TLR3</i> in HBV Clearance and HBV-Related Hepatocellular Carcinoma in a Chinese Male Population

Innate immunity can induce spontaneous hepatitis B surface antigen (HBsAg) seroclearance (SC) of hepatitis B virus (HBV) infection or transition towards an inactive carrier state. Toll-like receptor (TLR) 3 signalling has been linked to these processes. Alterations in the TLR3 gene might impair immune responses against HBV. In our study, we analysed the impact of the TLR3 polymorphisms rs3775291 and rs5743305 on the natural course of HBV infection. In this retrospective study, a Caucasian cohort of 621 patients with chronic HBV infection (CHB), 239 individuals with spontaneous HBsAg SC, and 254 healthy controls were enrolled. In the CHB group, 49% of patients were inactive carriers, and 17% were HBeAg-positive. The TLR3 rs3775291 A allele was associated with a reduced likelihood of spontaneous HBsAg SC and HBeAg SC, and an increased risk of developing chronic hepatitis B. In haplotype analysis, the haplotype including both risk variants rs3775291A and rs5743305A had the lowest likelihood of HBsAg SC. Further research in larger cohorts and functional analyses are needed to shed light on the impact of TLR3 signalling.

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“…Our observation regarding the association of TLR3 risk variants with HBsAg SC contradicts findings of previous studies 16 , 22 – 24 . Sa et al .…”

Section: Discussioncontrasting

confidence: 99%

“… 27 and Chen et al . 22 in Asian patients. Their studies suggest that the TLR3 SNP rs3775291 is a novel risk factor for HBV-related HCC.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population

Fischer

Koukoulioti

Schott

et al. 2018

Sci Rep

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“…According to the inclusion and exclusion criteria, 22 articles were included in this study, including five articles on TLR3 rs3775291 polymorphism and the risk of HBV [10][11][12][13][14] and 17 articles on IL-10 rs1800871 and susceptibility to HBV [16][17][18][19][25][26][27][28][29][30][31][32][33][34][35][36][37]. The detailed literature screening process was shown in Figure 1.…”

Section: Results Of Literature Retrievalmentioning

confidence: 99%

“…Rong et al [11] and Fischer et al [12] reported that allele T at the TLR3 rs3775291 loci increased the risk of HBV infection. However, other studies [13,14] suggested that its allele T was not related to the risk of HBV infection. IL-10, an important Th2 cytokine, plays an essential regulatory role in the immune process of HBV infection.…”

Section: Introductionmentioning

confidence: 94%

Association of TLR3 (rs3775291) and IL-10 (rs1800871) gene polymorphisms with susceptibility to Hepatitis B infection: A meta-analysis

Zhang

et al. 2020

Epidemiol. Infect.

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TLR3 and IL-10 play a crucial role in antiviral defence. However, there is a controversy between TLR3 rs3775291 and IL-10 rs1800871 polymorphisms and the risk of hepatitis B virus (HBV) infection. The purpose of this study is to explore the relationship between the two single nucleotide mutations and the risk of HBV infection by meta-analysis. Medline, EMBASE, Web of Science, CNKI, China Wanfang database were searched for the case-control studies on the relationship between TLR3 rs3775291 and IL-10 rs1800871 polymorphism and susceptibility to HBV, updated to June 2020. The data were analysed by Stata 15.0 software. A total of 22 articles were included. The results showed that in the analysis of IL10 rs1800871 polymorphism and the risk of HBV infection, the pooled OR was 1.21 (95% CI 1.06-1.37), 1.28 (95% CI 1.04-1.56) and 1.20 (95% CI 1.06-1.37) and 1.40 (95% CI 1.07-1.83) in the allele model (C vs. T), dominant model (CC+CT vs. TT), recessive model (CC vs. CT+TT) and homozygous model (CC vs. TT), respectively. There was no statistical significance in the heterozygote model. A subgroup analysis of the Asian population showed similar results. The analysis of TLR3 rs3775291 polymorphism and the risk of HBV showed that in the allele model (T vs. C), the pooled OR was 1.30 (95% CI 1.05-1.61). Except for the recessive model, no significances were found in other genetic models. In conclusion, TLR3 rs3775291 and IL-10 rs1800871 polymorphisms are associated with the risk of HBV. Allele C and genotype CC at IL10 rs1800871 loci, as well as allele T and genotype TT at TLR rs3775291 loci, may increase susceptibility to Hepatitis B infection.

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“…The RIG-I like receptors consist of three members, including DDX58/RIG-I (retinoic acid-inducible gene I), IFIH1/MDA-5 (melanoma differentiation-associated gene 5), and DHX58/LGP-2 (laboratory of genetics and physiology 2).They can sense viral RNA and induce powerful antiviral and pro-inflammatory gene expressions [ 32 – 34 ]. Among various Toll-like receptors (TLRs), TLR2 and TLR3 play a significant role in the modulation of virus-mediated innate immune response and trigger anti-viral signal pathways [ 36 – 39 ]. However, the mechanism and role of RNA editing changes during viral infection are yet to be completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive study on cellular RNA editing activity in response to infections with different subtypes of influenza a viruses

Cao

Cao²,

Huang

et al. 2018

BMC Genomics

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BackgroundRNA editing is an important mechanism that expands the diversity and complexity of genetic codes. The conversions of adenosine (A) to inosine (I) and cytosine (C) to uridine (U) are two prominent types of RNA editing in animals. The roles of RNA editing events have been implicated in important biological pathways. Cellular RNA editing activity in response to influenza A virus infection has not been fully characterized in human and avian hosts. This study was designed as a big data analysis to investigate the role and response of RNA editing in epithelial cells during the course of infection with various subtypes of influenza A viruses.ResultsUsing a bioinformatics pipeline modified from our previous study, we characterized the profiles of A-to-I and C-to-U RNA editing events in human epithelial cells during the course of influenza A virus infection. Our results revealed a striking diversity of A-to-I RNA editing activities in human epithelial cells in responses to different subtypes of influenza A viruses. The infection of H1N1 and H3N2 significantly up-regulated normalized A-to-I RNA editing levels in human epithelial cells, whereas that of H5N1 did not change it and H7N9 infection significantly down-regulated normalized A-to-I editing level in A549 cells. Next, the expression levels of ADAR and APOBEC enzymes responsible for A-to-I and C-to-U RNA editing during the course of virus infection were examined. The increase of A-to-I RNA editing activities in infections with some influenza A viruses (H1N1 and H3N2) is linked to the up-regulation of ADAR1 but not ADAR2. Further, the pattern recognition receptors of human epithelial cells infected with H1N1, H3N2, H5N1 and H7N9 were examined. Variable responsive changes in gene expression were observed with RIG-I like receptors and Toll like receptors. Finally, the effect of influenza A virus infection on cellular RNA editing activity was also analyzed in avian hosts.ConclusionThis work represents the first comprehensive study of cellular RNA editing activity in response to different influenza A virus infections in human and avian hosts, highlighting the critical role of RNA editing in innate immune response and the pathogenicity of different subtypes of influenza A viruses.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4330-1) contains supplementary material, which is available to authorized users.

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Gene Polymorphisms of TLR2 and TLR3 in HBV Clearance and HBV-Related Hepatocellular Carcinoma in a Chinese Male Population

Abstract: This study revealed that TLR2 rs3804100 and TLR3 rs3775291 polymorphisms may be protective factors for HBV-related HCC.

Cited by 14 publications

References 30 publications

Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population

Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population

Association of TLR3 (rs3775291) and IL-10 (rs1800871) gene polymorphisms with susceptibility to Hepatitis B infection: A meta-analysis

A comprehensive study on cellular RNA editing activity in response to infections with different subtypes of influenza a viruses

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