Abdel-Azeez Hala A, El-Okely Amir M
Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Egypt J Immunol. 2009;16(1):95-106.
The binding of advanced glycation end-products (AGEs) to their receptor (RAGE) may play an important role in the development of diabetic vascular complications. Circulating soluble RAGE (sRAGE) reflects tissue RAGE expression. We examined circulating sRAGE and RAGE -374 T/A gene promoter polymorphism in type 1 diabetic patients and explored their possible associations with the development of nephropathy. Fifty diabetic patients with disease duration >10 years and 20 age, sex and body mass index (BMI) matched healthy controls were included in the study. Diabetic patients were subdivided into 23 patients without nephropathy and 27 with nephropathy. All the studied individuals were subjected to the following investigations: fasting glucose, HbA1c, serum creatinine, lipid profile, albuminuria and sRAGE levels. The -374 T/A RAGE gene polymorphism was studied by PCR amplification and restriction fragment length polymorphism (RFLP) analysis. Our study reported significant increase in sRAGE in diabetic patients compared to controls and in diabetic patients with nephropathy compared to those without nephropathy (P < 0.001). sRAGE was significantly correlated with HbA1c, creatinine, albuminuria and atherogenic lipid profile. There were significant increase in the frequency of RAGE -374 A allele (T/A and/or A/A genotypes) in diabetic patients with nephropathy compared to those without nephropathy and control groups (P < 0.01). A allele was a risk factor for diabetic nephropathy (OR 2.36 & 95% CI 1.1-5.6). RAGE -374 A allele was associated with increased sRAGE levels, hypertension and increased creatinine concentration in diabetic patients. This study points to the possible role of sRAGE as a marker of early nephropathy in diabetic patients. Early testing for the RAGE gene -374 T/A could have merit in predicting risk of diabetic nephropathy later in life.
晚期糖基化终末产物（AGEs）与其受体（RAGE）的结合可能在糖尿病血管并发症的发生发展中起重要作用。循环可溶性RAGE（sRAGE）反映组织RAGE表达。我们检测了1型糖尿病患者循环中的sRAGE及RAGE -374 T/A基因启动子多态性，并探讨它们与肾病发生发展的可能关联。本研究纳入了50例病程超过10年的糖尿病患者以及20例年龄、性别和体重指数（BMI）相匹配的健康对照者。糖尿病患者被分为23例无肾病患者和27例有肾病患者。所有研究对象均接受以下检查：空腹血糖、糖化血红蛋白（HbA1c）、血清肌酐、血脂谱、蛋白尿和sRAGE水平。通过聚合酶链反应（PCR）扩增和限制性片段长度多态性（RFLP）分析研究RAGE -374 T/A基因多态性。我们的研究报告显示，与对照组相比，糖尿病患者的sRAGE显著升高；与无肾病的糖尿病患者相比，有肾病的糖尿病患者的sRAGE也显著升高（P < 0.001）。sRAGE与HbA1c、肌酐、蛋白尿和致动脉粥样硬化血脂谱显著相关。与无肾病的糖尿病患者及对照组相比，有肾病的糖尿病患者中RAGE -374 A等位基因（T/A和/或A/A基因型）的频率显著增加（P < 0.01）。A等位基因是糖尿病肾病的危险因素（比值比2.36，95%可信区间1.1 - 5.6）。RAGE -374 A等位基因与糖尿病患者sRAGE水平升高、高血压及肌酐浓度升高相关。本研究指出sRAGE可能作为糖尿病患者早期肾病标志物的作用。早期检测RAGE基因 -374 T/A可能有助于预测日后发生糖尿病肾病的风险。
