Abstract
BackgroundRecent data from human and animal studies have shown an upregulated expression of advanced glycosylation end product–specific receptor (RAGE) in human atherosclerotic plaques 1 and in retina, messangial, and aortic vessels, suggesting an important role of RAGE in the pathogenesis of atherothrombotic diseases. In the past few years, the relationship between RAGE polymorphisms (−429T/C, −374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; however, these studies have yielded contradictory results.MethodsPubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between RAGE polymorphisms and susceptibility to CHD. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 17 studies including 4343 patients and 5402 controls were involved in this meta-analysis. Overall, no significant results were observed for −429T/C (OR = 1.01, 95% CI: 0.92–1.12, P = 0.78), −374T/A (OR = 1.11, 95% CI: 0.98–1.26, P = 0.09) and G82S (OR = 1.12, 95% CI: 0.86–1.45, P = 0.41) polymorphism. In the stratified analyses according to ethnicity, sample size, CHD endpoint and Hardy-Weinberg status, no evidence of any gene-disease association was obtained.ConclusionsThis meta-analysis demonstrates that there is no association between the RAGE −429T/C, −374T/A and G82S polymorphisms and CHD.
Highlights
Coronary heart disease (CHD), including its most severe complication, myocardial infarction, is the leading cause of death in the industrialized world
Knowledge Infrastructure (CNKI) with keywords relating to the relevant gene (e.g. ‘‘receptor for advanced glycation end product’’, ‘‘RAGE’’, ‘‘advanced glycosylation end product–specific receptor’’, ‘‘AGER’’) in combination with words related to CHD (e.g. ‘‘coronary heart disease’’, ‘‘coronary artery disease’’, ‘‘myocardial infarction’’, ‘‘ischemic heart disease’’, ‘‘atherosclerosis’’, ‘‘arteriosclerosis’’, and ‘‘coronary stenosis’’)
For the 2374T/A polymorphism, 8 studies involved a total of 2605 cases and 3008 controls
Summary
Coronary heart disease (CHD), including its most severe complication, myocardial infarction, is the leading cause of death in the industrialized world. Traditional risk such as hypertension, diabetes mellitus, dyslipidemia and smoking can only explain approximately two-thirds of the observed clinical events. An important role of receptor for advanced glycation end product (RAGE) in the pathogenesis of vascular diseases has generated great interest. Irreversible advanced glycation end products (AGEs) are one class of RAGE ligands and occur at an increased level under conditions of hyperglycemia and in inflammatory environments [3,4]. In the past few years, the relationship between RAGE polymorphisms (2429T/C, 2374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; these studies have yielded contradictory results
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