Peng Wen Hui, Lu Lin, Wang Ling Jie, Yan Xiao Xiang, Chen Qiu Jing, Zhang Qi, Zhang Rui Yan, Shen Wei Feng
Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Arch Med Res. 2009 Jul;40(5):393-8. doi: 10.1016/j.arcmed.2009.06.008.
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).
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.
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.
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.
晚期糖基化终末产物受体（RAGE）与晚期糖基化终末产物的结合及随后的信号传导在糖尿病并发症的发生发展中起重要作用。内源性分泌型RAGE（esRAGE）可部分减轻这种病理生理效应。本研究旨在探讨中国2型糖尿病（T2DM）患者中RAGE基因多态性与血清esRAGE水平及冠状动脉疾病（CAD）之间的可能关联。
共纳入740例接受冠状动脉造影的连续性T2DM患者。冠状动脉粥样硬化的严重程度根据病变血管数量定义；通过聚合酶链反应确定69 bp插入/缺失情况，并通过聚合酶链反应-限制性片段长度多态性评估-429 T/C、-374A/T和G82S变异。
携带-429 T/C的C等位基因和G82S的G等位基因的基因型患者的esRAGE水平显著更高。在患有CAD的糖尿病患者中，82S等位基因还与肿瘤坏死因子-α和白细胞介素-6水平升高相关（所有p<0.05），但没有一种多态性或单倍型与CAD的存在和严重程度相关。
在中国T2DM患者中，RAGE的G82S和-429 T/C多态性与esRAGE的循环水平相关，但与CAD无关。
