Association of RAGE gene Gly82Ser polymorphism with coronary artery disease and ischemic stroke

Abstract

Background:The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and ischemic stroke (IS) remain controversial. The Gly82Ser polymorphism is located in the ligand-binding V domain of RAGE, suggesting a possible influence of this variant on RAGE function. The aim of the present study is to clarify the association between the RAGE Gly82Ser polymorphism and susceptibility to CAD and IS.Methods:Eligible studies were identified through a comprehensive literature search. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association of Gly82Ser polymorphism with CAD and IS risk. Fixed- or random-effects model was used depending on the heterogeneity between studies. A funnel plot and Egger linear regression test were applied to assess publication bias. We also performed subgroup analyses to investigate potential sources of heterogeneity.Results:A total of 16 eligible articles containing 18 studies were analyzed. The pooled analysis indicated that the Gly82Ser polymorphism significantly increased CAD risk in recessive and homozygous genetic models (SS vs GS + GG: OR = 1.34, 95% CI = 1.09–1.64; SS vs GG: OR = 1.38, 95% CI = 1.12–1.71). A significant association between the Gly82Ser polymorphism and IS risk was observed in all tested models except the heterozygous genetic model (GS + SS vs GG: OR = 1.20, 95% CI = 1.04–1.38; SS vs GS + GG: OR = 2.20, 95% CI = 1.74–2.78; SS vs GG: OR = 2.23, 95% CI = 1.72–2.91; S vs G: OR = 1.32, 95% CI = 1.05–1.65). Subgroup analysis suggested an association between CAD and IS risk and the Gly82Ser polymorphism in the Chinese population, but not in the non-Chinese population.Conclusions:The current meta-analysis suggests that the RAGE Gly82Ser polymorphism is associated with an increased risk of CAD and IS, especially in the Chinese population. However, better-designed studies with larger sample sizes are needed to validate the results.

Receptor for Advanced Glycation End Products (RAGE) and Mechanisms and Therapeutic Opportunities in Diabetes and Cardiovascular Disease: Insights From Human Subjects and Animal Models

“…For example, extensive studies in the Chinese Han population suggested that the rs2070600 SNP was significantly associated with increased risk of all-cause mortality and acute myocardial infarction (MI) (118). Ma and colleagues performed a meta-analysis of 16 eligible studies reporting on rs2070600 SNP and CVD; they reported an association between this SNP and coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese population, but not in non-Chinese populations (119). Until studies examining larger groups of subjects are examined to fully test this AGER SNP and potential relationships to CVD, studies of these specific populations in China may, therefore, shed light on mechanisms of RAGE-dependent predilections to CVD.…”

Association between miR‑499 rs3746444 polymorphism and the risk of ischemic stroke: A systematic review and meta‑analysis

“…MicroRNAs (miRNAs or miRs) play important roles in gene regulation; more than half of human genes are known to be regulated by miRNAs. miRNAs are also involved in numerous pathological pathways/process, such as the inflammatory response (1,2) and cancer development (3,4), as well as in the formation/development of ischemic stroke (IS) (5)(6)(7)(8)(9).…”

Genetic predisposition to ischaemic stroke by RAGE and HMGB1 gene variants in Chinese Han population

“…The genes encoding RAGE and HMGB1 are highly polymorphic, and more than twenty single nucleotide polymorphisms (SNPs) have been investigated [ 22 , 23 ]. Despite a large panel of RAGE and vascular disease-related genetic association studies, it remains unclear whether individuals possessing certain alleles are more susceptible to IS due their main or joint effects [ 24 - 27 ]. Therefore, we performed a case-control study to determine whether the variants of RAGE and HMGB1 genes are associated with IS susceptibility in a relatively large southern Chinese population.…”