TLR4 Asp299Gly (rs4986790) Polymorphism and Coronary Artery Disease: A Meta-Analysis

PeerJ. 2015 Nov 26;3:e1412. doi: 10.7717/peerj.1412. eCollection 2015.


Background. Previous studies have shown conflicting results on the association between toll-like receptor 4 (TLR4) Asp299Gly (rs4986790) polymorphism and coronary artery disease (CAD). The aim of this study was to evaluate the influence of TLR4 Asp299Gly polymorphism on CAD risk, CRP level and the number of stenotic coronary arteries, as well as to investigate whether G allele carriers would benefit more from statin treatment. Methods. PubMed, EMBASE, and CNKI databases were searched until May 2015. All the statistical tests were performed using R version 3.1.2. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the association between TLR4 Asp299Gly polymorphism and CAD risk, the number of stenotic vessels, and the incidence of cardiovascular events according to statin-treated patients. Weighted mean difference (WMD) was calculated for the association between Asp299Gly and CRP level. Results. Overall, 12 case-control studies with 10,258 cases and 5,891 controls were included, and no association of TLR4Asp299Gly polymorphism with CAD was found (G allele vs. A allele: OR = 0.97, 95% CI [0.81-1.17], P = 0.75; AA vs. GG + AG: OR = 0.97, 95% CI [0.80-1.18], P = 0.76; GG vs. AG + AA: OR = 1.08, 95% CI [0.57-2.02], P = 0.82; AG vs. AA + GG: OR = 1.03, 95% CI [0.85-1.25], P = 0.74). Also, no association was noted between Asp299Gly and CRP level (WMD = -0.10, 95% CI [-0.62, 0.41], P = 0.69). Furthermore, no synergistic effect of statin and 299Gly was reported (Statin_AA vs. Statin_

Ag/gg: OR = 1.12, 95% CI [0.41-3.09], P = 0.82). Discussion. This meta-analysis suggests no association of TLR4 Asp299Gly polymorphism with CAD and CRP level. It is further indicated that the G allele carriers may not benefit more from statin treatment. Further studies should include large sample size and high-quality literature to understand this issue in depth.

Keywords: Asp299Gly; C-reactive protein; Coronary artery disease; Polymorphism; Statin; Stenosis; Toll-like receptor 4.

Grant support

This work was supported by the National Natural Science Foundation of China (No. 81173399). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.