title: An interactive association of advanced glycation end-product receptor gene four common polymorphisms with coronary artery disease in northeastern Han Chinese.
abstract: BACKGROUND
  Growing 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.
  
  
  RESULTS
  This 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Xia
authors.forename: Lianjun
authors.initials: L
authors.lastname: Gao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
authors.forename: Yanzong
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003324:Coronary Artery Disease / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic