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The Roles of TLR Gene Polymorphisms in Atherosclerosis: A Systematic Review and Meta‐Analysis of 35,317 Subjects

Recently, the roles of toll like receptor (TLR) gene polymorphisms in atherosclerotic diseases were extensively investigated, with conflicting results. Therefore, we performed this study to better assess the relationship between TLR gene variants and atherosclerosis. Eligible studies were searched in PubMed, MEDLINE, EMBASE, Web of Science and CNKI. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate associations between TLR gene polymorphisms and atherosclerosis. A total of 40 studies covering 19,657 cases and 15,660 controls were finally included in our systematic review and meta‐analysis. Significant correlations with atherosclerosis susceptibility were found for the TLR1 rs5743551 polymorphism (dominant model: 95% CI 1.03–1.79; recessive model: 95% CI 0.28–0.97; allele model: 95% CI 1.07–1.69), TLR1 rs5743611 polymorphism (dominant model: 95% CI 0.56–0.98) and TLR6 rs5743810 polymorphism (recessive model: 95% CI 0.56–0.92) in overall analyses. Moreover, further subgroup analyses revealed that TLR4 rs1927911 polymorphism was significantly associated with the risk of cerebral infarction in the recessive model (95% CI 0.46–0.96), whereas TLR4 rs4986791 polymorphism was significantly correlated with susceptibility to atherosclerosis among Asians in the dominant (95% CI 1.58–6.66), additive (95% CI 0.13–0.69) and allele (95% CI 1.58–5.53) models. However, no positive results were found for the other 13 TLR polymorphisms. In conclusion, our findings indicate that most TLR gene polymorphisms may not be implicated in the pathogenesis of atherosclerosis, whereas certain TLR gene variations, such as rs5743551, rs5743611, rs5743810, rs4986791 and rs1927911, may serve as genetic biomarkers of atherosclerotic diseases.