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Review
. 2023 Jun 21;14(7):1311.
doi: 10.3390/genes14071311.

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

Marcos Jessé Abrahão Silva  1 , Caroliny Soares Silva  2 , Marcelo Cleyton da Silva Vieira  2 , Pabllo Antonny Silva Dos Santos  2 , Cristiane Cunha Frota  3 , Karla Valéria Batista Lima  4 , Luana Nepomuceno Gondim Costa Lima  4
Affiliations
Review

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

Marcos Jessé Abrahão Silva et al. Genes (Basel). .

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.

Keywords: TLR3; infectious diseases; single nucleotide polymorphism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart representing the stages of selection, eligibility, and inclusion of studies for analysis. Belém, PA, Brazil (2022).
Figure 2
Figure 2
Risk of bias summary: review authors’ judgments about each risk of bias item for each included study. Symbols in green mean compliance with the prerogative of that attribute investigated for that study, while the blank spaces (empty) demonstrate the gap for that information, and those in red indicate high methodological disagreement [13,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. Source: Elaborated by the authors with RevMan v5.4 software.
Figure 3
Figure 3
Forest plot of comparison about TLR3 SNP rs3775291 and risk of infections, outcome: SNP presence for genotypes CT/TT vs. CC. The OR of each study is represented on the plot as a square with the area of each square proportional to the weight of the corresponding study in the meta−analysis. Horizontal lines are the 95% CIs associated for the OR of each study. The bold values highlight the total frequency of cases and controls, as well as the overall OR and the 95% CI [13,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. Source: Elaborated by the authors with Comprehensive Meta−Analyses v2.2 software.
Figure 4
Figure 4
Funnel plot of comparison of the TLR3 SNP rs3775291 and infection risk for all studies included in the meta-analysis, outcome: SNP presence for genotypes. Circles represent the included published studies and should be symmetrically dispersed around the overall effect in the form of an inverted funnel. Studies with higher precision are closer to the true value and situated at the narrowest part of the funnel. On the Y-axis of the graph, there is a measure of dispersion, the standard error, which is influenced by the sample size of the study. The larger this value is, the greater the inaccuracy of the study. On the X-axis of the graph, there is the effect measure measured in the meta-analysis and the center line is the result of this (which is directed on the X-axis by the diamond). The lines that make up the outline of the funnel correspond to the 95% CI. Source: Elaborated by the authors with Comprehensive Meta−Analyses v2.2 software.
Figure 5
Figure 5
Bubble plot of the meta-regression analysis on the relationship between continent and the risk of infection based on the presence of the rs3775291 SNP. The size of the bubble is inversely related to the variance of the study. The solid line represents the linear regression (continent as the meta-independent variable). The two lines in the horizontal area between the main line correspond to the confidence intervals of the prediction. Source: Elaborated by the authors with Comprehensive Meta−Analyses v2.2 software.
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