Association of RAGE gene polymorphisms with coronary artery disease in the Korean population.
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.
Yoon
Se-Jung
SJ
Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.
Park
Sungha
S
Shim
Chi Young
CY
Park
Chan Mi
CM
Ko
Young-Guk
YG
Choi
Donghoon
D
Park
Hyun-Young
HY
Oh
Bermseok
B
Kim
HungTae
H
Jang
Yangsoo
Y
Chung
Namsik
N
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*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic