title: Association of RAGE gene polymorphisms with coronary artery disease in the Korean population.
abstract: OBJECTIVE
  AGEs (advanced glycation end products)-RAGE (receptor for advanced glycation end products) interaction in vessel wall may lead to inflammation, smooth muscle cell proliferation and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We focused on the putative association of five candidate RAGE gene polymorphisms on the risk of coronary artery disease in the Korean population.
  
  
  METHODS
  A total of 1555 male patients who underwent coronary angiography were enrolled in the study; 805 patients (mean age: 53.18+/-9.74 years) had normal coronary artery and 750 patients (mean age: 55.73+/-8.31 years) had significant coronary artery disease. Among the coronary artery disease patients, 269 had single-vessel disease (35.87%), 242 had two-vessel disease (32.27%) and 239 had three-vessel disease (31.87%). The genotypes of RAGE were determined by the methods of single base extension with amplifying primers and probes for TaqMan. Genotype analysis was performed on five single nucleotide polymorphisms of the RAGE gene, namely -443T>C, -388T>A, -257G>A, +557G>A and +1704G>T. Analysis for the association with coronary artery disease was performed.
  
  
  RESULTS
  Analysis of four single nucleotide polymorphisms, except +557G>A (G82S), with regard to the association with coronary artery disease was not significant. Only the +557 gene allele (G/A) showed significant association with coronary artery disease (coronary artery disease vs. normal; G allele: 0.87 vs. 0.84, A allele: 0.13 vs. 0.16, P=0.0326). The +557G>A (G82S) showed strong tendency of association with coronary artery disease (coronary artery disease vs. normal; GG: 75.2 vs. 69.8%, GA: 23.2 vs. 28.6%, AA: 1.6 vs. 1.6%, P=0.0524). The presence of AA or GA genotype, assuming codominant effect of the A allele, was independently associated with decreased risk of coronary artery disease when controlled for age, body mass index, smoking and diabetes mellitus [odds ratio=0.749 (95% confidence interval, 0.579-0.969), P=0.0280]. Subgroup analysis demonstrated the significant protective effect of AA or GA genotype in nondiabetic patients as well [odds ratio=0.741 (0.570-0.962), P=0.0244].
  
  
  CONCLUSIONS
  The results of this large population study demonstrate that the AA/GA genotypes of the RAGE +557G>A polymorphism are associated with a significantly decreased risk of significant coronary artery disease. Other polymorphisms of RAGE were not significantly associated with the risk of coronary artery disease in this study population.
authors.affiliation: Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Se-Jung
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Shim
authors.forename: Chan Mi
authors.initials: CM
authors.lastname: Park
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Ko
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.forename: HungTae
authors.initials: H
authors.lastname: Kim
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Namsik
authors.initials: N
authors.lastname: Chung
mesh_terms: D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics*; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic