Meta-analysis of the association between toll-like receptor gene polymorphisms and hepatitis C virus infection

Yuxuan Du; Shumin Li; Xinyu Wang; Jialu Liu; Yan Gao; Weimiao Lv; Ping Liu; Haiyan Huang; Junwen Luan; Leiliang Zhang

doi:10.3389/fmicb.2023.1254805

Meta-analysis of the association between toll-like receptor gene polymorphisms and hepatitis C virus infection

Front Microbiol. 2023 Oct 5:14:1254805. doi: 10.3389/fmicb.2023.1254805. eCollection 2023.

Authors

Yuxuan Du¹, Shumin Li¹, Xinyu Wang¹, Jialu Liu¹, Yan Gao¹, Weimiao Lv¹, Ping Liu², Haiyan Huang¹, Junwen Luan¹, Leiliang Zhang¹

Affiliations

¹ School of Clinical and Basic Medical Sciences & Institute of Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
² School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Abstract

Objective: The objective of this study is to investigate the association between toll-like receptor (TLR) 3/7 gene polymorphisms and the infection by hepatitis C virus (HCV).

Methods: PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang Data, and SinoMed were searched to identify studies focusing on the association between the TLR3 rs3775290 or the TLR7 rs179008 single nucleotide polymorphisms (SNPs) and the HCV infection. All the related articles were collected from the inception of each database to 15 January 2023. Our meta-analysis was conducted using the allelic model, the dominant model, and the recessive model. Outcomes were presented by odds ratio (ORs) and 95% confidence interval (95%CI). The heterogeneity across studies was assessed by the I² test. A subgroup analysis was performed to explore the source of heterogeneity. Funnel plots were drawn to assess the risk of publication bias. Review Manager 5.4 was used for statistical analysis.

Results: Ten articles were finally included, among which six studies were analyzed for rs3775290 and five studies were analyzed for rs179008. Studies relating to rs3775290 included 801 patients and 1,045 controls, whereas studies relating to rs179008 included 924 patients and 784 controls. The results of the meta-analysis showed that there is no significant association between rs3775290 gene polymorphism and HCV infection (T vs. C: OR = 1.12, 95%CI 0.97-1.30; TT+CT vs. CC: OR = 1.20, 95%CI 0.73-1.96; TT vs. CT+CC: OR = 1.13, 95%CI 0.68-1.89). The recessive model showed that rs179008-T allele homozygotes had an 89% increased risk of infection by HCV compared with rs179008-A allele carriers (TT vs. AT+AA: OR = 1.89, 95%CI 1.13-3.16). The results of the subgroup analysis demonstrated that the characteristics of the control population may serve as an important source of heterogeneity. In the African populations, individuals with homozygous rs179008-T alleles had a higher risk of infection by HCV than rs179008-A allele carriers (OR = 2.14, 95%CI 1.18-3.87). We did not find that this difference existed in the European populations (OR = 1.24, 95%CI 0.43-3.56).

Conclusion: There is no significant association between rs3775290 single nucleotide polymorphism and the infection by HCV. Individuals with homozygous rs179008-T alleles have a higher risk of an infection by HCV than rs179008-A allele carriers, which is statistically significant in the African populations.

Keywords: hepatitis C (HCV); meta-analysis; single nucleotide polymorphisms (SNP); toll-like receptor (TLR); virus.

Publication types

Review

Grants and funding

This research was funded by the Natural Science Foundation General Project of Shandong Province (ZR2020MH299), the Student Research Training Program of Shandong First Medical University (2022104391196 and 202310439014), Academic Promotion Programme of Shandong First Medical University (2019LJ001), and the Undergraduate Science and Technology Innovation Plan of International Class of Clinical Medicine in Shandong First Medical University (KC2021-014).