Abstract
Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.
Highlights
Epidemiological studies have strongly supported a pivotal role for inflammatory, innate immune, and adaptive immune mechanisms in the pathogenesis of atherosclerosis [1,2]
Inclusion criteria We independently evaluated eligible articles on the basis of the following inclusion criteria: 1) evaluation of Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility, 2) case-control studies, and 3) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI)
Researchers have focused on numerous polymorphisms and mutations in genes that are related to atherosclerosis
Summary
Epidemiological studies have strongly supported a pivotal role for inflammatory, innate immune, and adaptive immune mechanisms in the pathogenesis of atherosclerosis [1,2]. The importance of Toll-like receptors (TLRs) in antimicrobial responses is established, the role in atherosclerotic disease is not well understood [3,4]. TLR4 is predominantly known for its role as an important mediator of innate immune response and has been implicated in the initiation, progression, and plaque destabilization stages of atherosclerosis [5]. It is logical to consider that TLR4-mediated signaling might be a potential target for intervention in the initiation and progression of coronary heart disease (CHD). Variants in the gene encoding TLR4 may affect the development of atherosclerosis accompanied by an impaired signal transduction, but the responsible polymorphisms remain inconclusive [6,7]. A single nucleotide polymorphism TLR4 Asp299Gly (rs4986790) has been reported to be associated with lower levels of proinflammatory serum markers, many of which have been implicated in atherosclerosis. We performed a meta-analysis of the eligible studies to derive a more precise estimation of the association
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