Abstract
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.
Highlights
Coronary artery disease (CAD), resulting from atherosclerosis (AS), has become the leading cause of disability and death globally (Murray et al, 2012)
As most of the variations, Asp299Gly is in the leucine-rich repeat (LRR) domain of Exon 3 which is associated with the recognition of pathogen-associated molecular patterns (PAMPs) (Smirnova et al, 2000)
Inclusion and exclusion criteria The inclusion criteria for the studies about the association between toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary artery disease (CAD) were as follows: (a) published case–control studies, and the control group should be the population without CAD; (b) clear diagnosis criteria of CAD; (c) studies supplied the number of individual genotypes in CAD cases and controls; (d) sufficient data for estimating an odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI); (e) written in English or Chinese
Summary
Coronary artery disease (CAD), resulting from atherosclerosis (AS), has become the leading cause of disability and death globally (Murray et al, 2012). C-reactive protein (CRP) serves as a useful biomarker of inflammatory diseases, and is considered as an independent risk factor to predict first and recurrent cardiovascular events; its level with TLR4 Asp299Gly has gained enormous attention (Kiechl et al, 2002; Edfeldt et al, 2004; Kolek et al, 2004; Netea et al, 2004; Hernesniemia et al, 2006; Beijk et al, 2010). 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. This meta-analysis suggests no association of TLR4 Asp299Gly polymorphism with CAD and CRP level. Further studies should include large sample size and high-quality literature to understand this issue in depth
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