| Division of Cardiology¹,Cardiovascular Research Institute and Genome Center, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine ²,Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health³ |
| Se-Jung Yoon, Sungha Park¹,Chanmi Park², Young-Guk Ko¹,Donghoon Choi¹,Hyun-Young Park ³,Yangsoo Jang¹,Namsik Chung ¹ |
Background:The receptor for advanced glycation end products(RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules and engages diverse ligands relevant to distinct pathological process. RAGE mediates vascular inflammation through activation of myriad of inflammatory mediators. We focused on the putative association of RAGE gene polymorphism on the risk of coronary artery disease(CAD) in the Korean population.
Methods: A total 1467 male patients who underwent coronary angiography were enrolled in the study; 717 patients (mean age:52.18±9.76) had normal coronary artery and 750 patients(mean age:55.73±8.31) had significant coronary artery disease. Among the coronary artery disease patients, there were 269 1- VD(35.87%), 242 2-VD(32.27%), and 239 3-VD(31.87%).The genotypes of RAGE was determined by the methods of single base extension with amplifying primers and probes for TaqMan. Genotype analysis was performed on 6 SNPs of the RAGE gene, namely -1106T>C, -443 T>C, -388T>A, -257G>A, +557G>A, +1704G>T. Analysis for the association with coronary artery disease was performed.
Results: Analysis of -1106T>C, -443 T>C, -388T>A, -257G>A, +1704G>T regarding the association with coronary artery disease was not significant. Among the SNPs analyzed, only the +557G>A showed significant association with coronary artery disease(CAOD vs Normal; GG:75.2 vs 69.6% , GA:23.2 vs 28.9% , AA:1.6 vs 1.5% , p-value =0.0459). 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, BMI and smoking [OR=0.58(0.37-0.92), P-value = 0.019]. Subgroup analysis demonstrated the significant protective effect of AA or GA genotype in non diabetic patients as well[OR=0.53(0.32-0.87),P-value = 0.012]. Conclusions: The results of this study demonstrate that the AA/GA genotype of the RAGE +557G>A polymorphism is associated with significantly decreased risk of significant CAD. Other polymorphisms of RAGE were not significantly associated with the risk of CAD in this study population.This work was supported by a grant of Ministry of Health and Welfare, Republic of Korea(00-PJ6-PG5-23-0001)
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