RAGE gene polymorphisms are associated with circulating levels of endogenous secretory RAGE but not with coronary artery disease in Chinese patients with type 2 diabetes mellitus.
OBJECTIVE
Engagement of the receptor for advanced glycation end products (RAGE) with advanced glycation end products and subsequent signaling play an important role in the development of diabetic complications. This pathophysiological effect was mitigated partially by endogenous secretory RAGE (esRAGE). The present study aimed to explore the possible association of RAGE polymorphism with serum esRAGE level and coronary artery disease (CAD) in Chinese patients with type 2 diabetes mellitus (T2DM).


METHODS
A total of 740 consecutive patients with T2DM undergoing coronary angiography were enrolled. The severity of coronary atherosclerosis was defined as the number of diseased vessels; 69 bp insertion/deletion was determined by polymerase chain reactions, and -429 T/C, -374A/T and G82S variants were assessed by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
Patients with genotypes carrying C allele of -429 T/C and G allele of G82S had significantly higher esRAGE levels. 82S allele was also associated with increased tumor necrosis factor-alpha and interleukin-6 levels in diabetic patients with CAD (all p <0.05), but none of the polymorphisms or haplotypes was related to the presence and severity of CAD.


CONCLUSIONS
G82S and -429 T/C polymorphisms of RAGE were associated with the circulating levels of esRAGE but not with CAD in Chinese patients with T2DM.
Peng
Wen Hui
WH
Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Lu
Lin
L
Wang
Ling Jie
LJ
Yan
Xiao Xiang
XX
Chen
Qiu Jing
QJ
Zhang
Qi
Q
Zhang
Rui Yan
RY
Shen
Wei Feng
WF
D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism; D002681:China; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
C508600:IL6 protein, human; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein