Genetics of diabetic nephropathy in type 2 DM: candidate gene analysis for the pathogenic role of inflammation
Genetics of diabetic nephropathy in type 2 DM: candidate gene analysis for the pathogenic role of inflammation
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DOI：
10.1111/j.1440-1797.2005.00454.x
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发表时间：
2005-10-01
期刊：
影响因子：
2.5
通讯作者：
Chung, JH
中科院分区：
文献类型：
--
作者：
Lee, SH;Lee, TW;Chung, JH
高血压、血糖控制不良和白蛋白尿是糖尿病肾病的已知危险因素，但这些因素不能解释进展为肾衰竭的速率的所有个体间变异性。近年来的研究表明，遗传易感性影响2型糖尿病（DM）患者高血糖引起的肾毒性。我们回顾了目前关于遗传学与2型糖尿病肾病关系的知识。然而，结果是不确定的，糖尿病肾病的遗传决定因素尚未完全了解。此外，2型糖尿病肾病的遗传背景被认为比1型糖尿病更复杂。近年来的研究表明，炎症是2型糖尿病及其并发症的重要组成部分。我们推测，在高糖环境中，全身和/或肾内炎症的增加在2型糖尿病患者肾病的发病机制中是重要的。为了研究炎症对糖尿病肾病的影响，我们研究了2型糖尿病患者炎症细胞因子和趋化因子编码基因的几种多态性。其中IL-1 β基因-511 C/T、IL-1受体拮抗剂基因-1Ra、肿瘤坏死因子-α基因-308 G/A与肾功能衰竭的危险性显著相关。此外，其中一些与NCB 1或西方文献报道的结果有显著差异，提示炎症可能在2型糖尿病肾病中起致病作用。深入了解糖尿病肾病的遗传易感因素不仅有助于糖尿病患者的识别，而且有助于揭示糖尿病肾病的发病机制。
Hypertension, poor glycemic control and albuminuria are well known risk factors for diabetic nephropathy, but these factors do not explain all of the inter-individual variabilities in the rate of progression to kidney failure. Recent evidence showed that genetic predisposition affected the hyperglycemia-induced nephrotoxicity in patients with type 2 diabetes mellitus (DM). We reviewed the present state of knowledge concerning the relationship between genetics and diabetic nephropathy in type 2 DM. However, the results are inconclusive and the genetic determinants of diabetic nephropathy are not fully understood. In addition, genetic background of nephropathy in type 2 DM was thought to be more complex than in type 1 DM. Recent studies suggested that the inflammation would be an essential component of type 2 DM and its complications. We postulated that increased systemic and/or intrarenal inflammation in high glucose milieu is important in the pathogenesis of nephropathy in patients with type 2 DM. To investigate the impact of inflammation on diabetic nephropathy, we studied several polymorphisms in genes encoding inflammatory cytokine and chemokine in patients with type 2 DM. Among them, -511 C/T in interleukin-1 beta (IL-1 beta), tandem repeat in IL-1 receptor antagonist (IL-1 Ra), -308 G/A in tumour necrosis factor-alpha (TNF-alpha) were significantly associated with an increased risk of kidney failure. In addition, some of them were remarkably different from those previously reported in the NCBl or literature based on the western population.Our results suggest that inflammation could play a pathogenic role in diabetic nephropathy in type 2 DM. A better understanding of genetic factors predisposing to diabetic nephropathy would not only help to identify diabetic patients at risk, but also be helpful to unveil the pathogenesis of DN.