The Relationship between TLR3 rs3775291 Polymorphism and Infectious Diseases: A Meta-Analysis of Case-Control Studies

As the host's first line of defense against pathogens, Toll-like receptors (TLRs), such as the TLR3, are genes encoding transmembrane receptors of the same name. Depending on their expression, TLRs cause a pro- or anti-inflammatory response. The purpose of the article was to determine whether there is an association between the Toll-like receptor 3 (TLR3) rs3775291 Single Nucleotide Polymorphism-SNP and susceptibility to infections. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered in PROSPERO under the code CRD42023429533. A systematic search for relevant studies was performed using PubMed, Scopus, SciELO, Google Scholar, and Science Direct by the MeSH descriptors and the Boolean Operator "AND": "Infections"; "TLR3"; "SNP", between January 2005 and July 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for genotypic comparison assuming a dominant genetic model (CT + TT vs. CC). A meta-analysis of 18 studies consisting of 3118 cases and 4368 controls found a significant association for risk between the presence of the TLR3 SNP rs3775291 and infections as part of the general analysis (OR = 1.16, 95% CI = 1.04-1.28, p = 0.004). In the subgroups of continents, the SNP had a protective role in Europe for 1044 cases and 1471 controls (OR = 0.83, 95% CI = 0.70-0.99, p = 0.04); however, the Asian (for 1588 patients and 2306 controls) and American (for 486 patients and 591 controls) continents had an increase in infectious risk (OR = 1.37, 95% CI = 1.19-1.58, p < 0.001; OR = 1.42, 95% CI = 1.08-1.86, and p = 0.01, respectively). Heterogeneity between studies was detected (I-2 = 58%) but was explained in meta-regression by the subgroup of continents itself and publication bias was not evident. The results of the meta-analysis suggest a significant association between the TLR3 rs3775291 polymorphism and susceptibility to infections. Thus, when analyzing subgroups, the Asian and American continents showed that this SNP confers a higher risk against infections in a dominant genotypic model. Therefore, more studies are necessary to fully elucidate the role of TLR3 rs3775291 in infections.