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

Abstract

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 (I2 = 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.

Analysis of associations between the TLR3 SNPs rs3775291 and rs3775290 and COVID-19 in a cohort of professionals of Belém-PA, Brazil

“…The frequency of the mutant allele (T) of SNP rs3775291 previously reported by several studies registered at the National Center for Biotechnology Information (NCBI) in Latin American populations was very different from that found in the present research in a cohort of the Amazonian population in Brazil. The Latin American frequency of the presence of this SNP mutant allele varies between 0 and 28%, while in the cohort of this study, only approximately 2% of the (T) allele was found (National Center of Biotechnology Information, 2023b; Silva et al, 2023b). This distribution of alleles related to the genotyping of this SNP in the Amazonian cohort was different even in relation to other research published in other Brazilian regions (Santos et al, 2019;Singh and Samani, 2022).…”

“…Regarding the literary scenario on associations between the investigated TLR3 SNPs and infections, several studies have already linked the rs3775291 SNP with infectious diseases ( Lee et al., 2013 ; Chen et al., 2017b ; Santos et al., 2019 ; Posadas-Mondragón et al., 2020 ; Redondo et al., 2022a ). A recent meta-analysis by ( Silva et al, 2023a ; Silva et al, 2023b ) summarized data found by primary research in several countries involving this SNP and infectious diseases. As a result, the authors found that the mutant allele (T) was linked to a 0.16-fold increased risk of virus infection worldwide ( Silva et al., 2023b ).…”

“…A recent meta-analysis by ( Silva et al, 2023a ; Silva et al, 2023b ) summarized data found by primary research in several countries involving this SNP and infectious diseases. As a result, the authors found that the mutant allele (T) was linked to a 0.16-fold increased risk of virus infection worldwide ( Silva et al., 2023b ). One of the infectious diseases most studied to look for associations with this SNP was hepatitis B, caused by HBV (a type of DNA chain virus) ( Wu et al., 2007 ; Li and Zheng, 2013 ; Geng et al., 2016 ).…”

Assessment of the Risk Impact of SARS-CoV-2 Infection Prevalence between Cats and Dogs in America and Europe: A Systematic Review and Meta-Analysis

“…The Cochrane Chi-Square test and the I-square measure (I 2 ) were used to determine the considerable statistical difference ( p ≤ 0.05 was considered a significant threshold) [ 19 ]. The correlation test for Begg and a funnel plot were used to examine the potential for publication bias ( p ≤ 0.05 was considered statistically significant) [ 20 ].…”

Analysis of Epidemiological Factors and SNP rs3804100 of TLR2 for COVID-19 in a Cohort of Professionals Who Worked in the First Pandemic Wave in Belém-PA, Brazil

“…TLRs play a key role in generating and maintaining the innate immune response, in addition to guiding the adaptive immune response in infections. Therefore, SNPs in these genes can generate different levels of receptor expression, generating uncoordinated immune responses through excessive or reduced cytokine production [21][22][23].…”