The-374 T/A polymorphism in the gene encoding RAGE is associated with diabetic nephropathy and retinopathy in type 1 diabetic patients
The-374 T/A polymorphism in the gene encoding RAGE is associated with diabetic nephropathy and retinopathy in type 1 diabetic patients
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DOI：
10.1007/s00125-006-0412-3
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发表时间：
2006-11-01
期刊：
影响因子：
8.2
通讯作者：
Agardh, C. -D.
中科院分区：
文献类型：
--
作者：
Lindholm, E.;Bakhtadze, E.;Agardh, C. -D.
AGE受体（receptor for AGE，AGE）主要是一种细胞内信号转导分子或促炎肽，对炎症和自身免疫性疾病可能具有重要意义。本研究旨在探讨AGER基因-374 T/A多态性与糖尿病类型及并发症的关系。方法对867例1型糖尿病患者、2,467例2型糖尿病患者和205例非糖尿病对照者进行AGER-374 T/A基因多态性检测。结果AGER基因多态性与HLA-DQB1基因型及糖尿病并发症的发生有关。1型糖尿病患者AGER-374 A/A或T/A基因型频率高于2型糖尿病患者（51.1 vs 44.9%，p = 0.002）和对照组（51.1 vs 47.6%，p = 0.0006）。HLA-374 T/A多态性与HLA-DQB1基因型相关; HLA风险基因型患者的A/A或T/A基因型频率高于其他HLA-DQB1基因型患者（60.3% vs 40.3%，p <0.00001）。在1型糖尿病患者中，A/A或T/A基因型在糖尿病肾病患者中的频率高于无糖尿病肾病患者（61.1 vs 46.8%，p = 0.006），在有视力威胁性视网膜病变患者中的频率高于无糖尿病肾病患者（56.1 vs 47.6%，p = 0.03）。在HbA（1c）值低于中位数的2型糖尿病患者中，糖尿病肾病患者的T/T基因型比无糖尿病肾病患者更常见（54.3% vs 38.2%，p = 0.02）。结论/解释我们的结果显示AGER-374 T/A多态性与1型糖尿病之间存在关联。这种关联是HLA-DQB1依赖性的。该多态性与1型和2型糖尿病的糖尿病肾病相关，在后者中以HbA（1c）依赖的方式，也与1型糖尿病患者的视力威胁性视网膜病变相关。
Aims/hypothesis The receptor for AGE (RAGE) is considered to be mainly an intracellular signal-transducer or pro-inflammatory peptide of possible importance for inflammation and autoimmune diseases. Our aim was to study whether the -374 T/A polymorphism in the gene encoding RAGE (AGER) is associated with diabetes type and presence of diabetic complications. Methods The AGER -374 T/A polymorphism was genotyped in 867 type 1 diabetic patients, 2,467 type 2 diabetic patients and 205 non-diabetic control subjects of Scandinavian origin. Results AGER polymorphism was related to different HLA-DQB1 genotypes and the presence of diabetic complications. Type 1 diabetic patients had a higher frequency of the AGER -374 A/A or T/A genotypes than type 2 diabetic patients (51.1 vs 44.9%, p=0.002) and control subjects (51.1 vs 47.6%, p=0.0006). The RAGE -374 T/A polymorphism was associated with HLA-DQB1 genotypes; patients with HLA risk genotypes had a higher frequency of the A/A or T/A genotypes than patients with other HLA-DQB1 genotypes (60.3 vs 40.3%, p < 0.000001). In type 1 diabetic patients, the frequency of the A/A or T/A genotypes was higher in patients with diabetic nephropathy than without (61.1 vs 46.8%, p=0.006) and with sight-threatening retinopathy than without (56.1 vs 47.6%, p=0.03). In type 2 diabetic patients with HbA(1c) values below the median, the T/T genotype was more frequent in patients with diabetic nephropathy than without (54.3 vs 38.2%, p=0.02). Conclusions/interpretation Our results show an association between the AGER -374 T/A polymorphism and type 1 diabetes. This association was HLA-DQB1-dependent. The polymorphism was associated with diabetic nephropathy in both type 1 and type 2 diabetes, in an HbA(1c)-dependent manner in the latter group, and also with sight-threatening retinopathy in type 1 diabetic patients.