An Interactive Association of Advanced Glycation End-Product Receptor Gene Four Common Polymorphisms with Coronary Artery Disease in Northeastern Han Chinese

Abstract

BackgroundGrowing evidence indicates that advanced glycation end-product receptor (RAGE) might play a contributory role in the pathogenesis of coronary artery disease (CAD). To shed some light from a genetic perspective, we sought to investigate the interactive association of RAGE gene four common polymorphisms (rs1800625 or T-429C, rs1800624 or T-374A, rs2070600 or Gly82Ser, and rs184003 or G1704A) with the risk of developing CAD in a large northeastern Han Chinese population.Methodology/Principal FindingsThis was a hospital-based case-control study incorporating 1142 patients diagnosed with CAD and 1106 age- and gender-matched controls. All individuals were angiographically confirmed. Risk estimates were expressed as odds ratio (OR) and 95% confidence interval (CI). Overall there were significant differences in the genotype and allele distributions of rs1800625 and rs184003, even after the Bonferroni correction. Logistic regression analyses indicated that rs1800625 and rs184003 were associated with significant risk of CAD under both additive (OR = 1.20 and 1.23; 95% CI: 1.06–1.37 and 1.06–1.42; P = 0.006 and 0.008) and recessive (OR = 1.75 and 2.39; 95% CI: 1.28–2.40 and 1.47–3.87; P<0.001 and <0.001) models after adjusting for confounders. In haplotype analyses, haplotypes C-T-G-G and T-A-G-T (alleles in order of rs1800625, rs1800624, rs2070600 and rs184003), overrepresented in patients, were associated with 52% (95% CI: 1.19–1.87; P = 0.0052) and 63% (95% CI: 1.14–2.34; P = 0.0075) significant increases in adjusted risk for CAD. Further interactive analyses identified an overall best multifactor dimensionality reduction (MDR) model including rs1800625 and rs184003. This model had a maximal testing accuracy of 0.6856 and a cross-validation consistency of 10 out of 10 (P = 0.0016). The validity of this model was substantiated by classical Logistic regression analysis.ConclusionsOur findings provided strong evidence for the potentially contributory roles of RAGE multiple genetic polymorphisms, especially in the context of locus-to-locus interaction, in the pathogenesis of CAD among northeastern Han Chinese.

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

“…Finally, 16 articles meeting the inclusion criteria were preserved. [17–32] A flow diagram of the literature selection process is shown in Fig. 1.…”

“…[16] Some studies in humans and animals have yielded conflicting results concerning the potential role of the RAGE Gly82Ser polymorphism in the pathogenesis of atherosclerosis. Several studies have indicated that Gly82Ser polymorphism is a possible risk factor for the development of CAD, [17,18] while others failed to specifically link this variant to CAD. [19,20] Meanwhile, the role of Gly82Ser polymorphism in IS susceptibility remains controversial.…”

Risk-Association of DNMT1 Gene Polymorphisms with Coronary Artery Disease in Chinese Han Population

“…The haplotype frequencies of five examined polymorphisms in DNMT1 gene were estimated as previously reported [ 22 ]. Only haplotype with frequency ≥3% was considered in haplotype analyses.…”

Association of 5 Well-Defined Polymorphisms in the Gene Encoding Transforming Growth Factor-β1 With Coronary Artery Disease Among Chinese Patients With Hypertension

“…21,22 In fact, all study patients in this study are local residents of Han Chinese descent from northeast China, and they are characterized by genetic homogeneity and geographic stability, and are probably more uniform in their environmental exposures, including the habitual dietary intake of high salt and high fat. 15 Even so, the results of this association study must be viewed with great caution given that our effect estimates were based on 679 patients with CAD and 686 controls, this sample size possibly being insufficient to draw a firm conclusion. However, a priori power calculation of our sample size convinced us to have >94% power to detect the significant genetic markers of realistic effect sizes.…”

“…14,15 Written informed consent was obtained from each patient at enrollment. This study received approval from the ethics committee of Dalian Medical University and was conducted in agreement with the guidelines of Declaration of Helsinki.…”