Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings: A protocol for systematic review and meta-analysis

Abstract

Background: To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies. Method: Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore. Results: A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 - 196 to -174Ins/Del (odds ratio [OR]=1.562; P=.002), TLR4 rs4986790 (OR=2.05; P=.002), TLR3 rs3775291 (OR=0.25; P=.03), TLR7 rs179008 (P=.002), TLR7 rs2074109 (OR=0.27, P=.019) were found associated with HIV infection. TLR2 -196 to - 174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR=1.25, PA=.02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR=1.50, PA=.04). Conclusions: The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection. Abbreviations: 95% CIs = 95% confidence intervals, AIDS = acquired immunodeficiency syndrome, FPRP = false-positive report probability, GWAS = genome-wide association studies, HIV = human immunodeficiency virus, HWE = Hardy-Weinberg equilibrium, IRF-3 = interferon regulatory factor-3, NOS = Newcastle-Ottawa quality assessment scale, OR = odds ratio, SNPs = singlenucleotide polymorphism, TLR = toll-like receptor, TSA = trial sequential analysis.