Hofmann Marion A, Yang Qiong, Harja Evis, Kedia Prashant, Gregersen Peter K, Cupples L Adrienne, Schmidt Ann Marie, Hudson Barry I
Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, P and S 17-401, New York, NY 10032, USA.
Atherosclerosis. 2005 Oct;182(2):301-5. doi: 10.1016/j.atherosclerosis.2005.02.006.
The receptor for advanced glycation end-products (RAGE) is expressed to enhance degrees in human atherosclerotic plaques and co-localizes with inflammatory and pro-oxidant mediators in the vulnerable regions of the plaque. Previous studies highlighted a number of variants in the gene encoding the receptor, including a Gly to Ser substitution at amino acid 82 within the ligand-binding domain of RAGE. The Ser82 allele enhanced ligand-binding affinity and increased ligand-stimulated generation of inflammatory mediators in transfected cells and human monocytes compared to the common RAGE Gly82 allele. Thus it was logical to test the hypothesis that increased prevalence of the Gly82Ser polymorphism was associated with cardiovascular events in the Framingham offspring study (n=1632). Our analyses revealed that the Gly82Ser RAGE polymorphism did not demonstrate any association with the incidence of cardiovascular disease in diabetic or non-diabetic subjects (Gly82 96%, Ser82 4%). Analysis of specific manifestations of cardiovascular disease, including coronary heart disease (CHD), cardiovascular disease (CVD), myocardial infarction (MI) and ischemic disease (ISD) revealed no association with RAGE genotype. Further studies are required on other more prevalent genetic variants of RAGE and cardiovascular disease.
晚期糖基化终末产物受体（RAGE）在人类动脉粥样硬化斑块中的表达程度增强，并在斑块的易损区域与炎症和促氧化介质共定位。先前的研究强调了该受体编码基因中的一些变体，包括RAGE配体结合域内第82位氨基酸处的甘氨酸（Gly）到丝氨酸（Ser）的替换。与常见的RAGE Gly82等位基因相比，Ser82等位基因增强了配体结合亲和力，并增加了转染细胞和人类单核细胞中配体刺激的炎症介质生成。因此，在弗雷明汉后代研究（n = 1632）中检验Gly82Ser多态性患病率增加与心血管事件相关这一假设是合乎逻辑的。我们的分析显示，Gly82Ser RAGE多态性与糖尿病或非糖尿病受试者的心血管疾病发病率无任何关联（Gly82占96%，Ser82占4%）。对心血管疾病的具体表现进行分析，包括冠心病（CHD）、心血管疾病（CVD）、心肌梗死（MI）和缺血性疾病（ISD），结果显示与RAGE基因型无关联。需要对RAGE的其他更常见基因变体与心血管疾病进行进一步研究。
