Lee Sang-Ho, Lee Tae Won, Ihm Chun-Gyoo, Kim Myung Jae, Woo Jeoung-Taek, Chung Joo-Ho
Department of Nephrology, College of Medicine, Kyung-Hee University, Dongdaemun-Gu, Seoul, Korea.
Nephrology (Carlton). 2005 Oct;10 Suppl:S32-6. doi: 10.1111/j.1440-1797.2005.00454.x.
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-1beta (IL-1beta), tandem repeat in IL-1 receptor antagonist (IL-1Ra), -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 NCBI 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.
高血压、血糖控制不佳和蛋白尿是糖尿病肾病众所周知的危险因素，但这些因素并不能解释所有个体在肾衰竭进展速度上的差异。最近的证据表明，遗传易感性会影响2型糖尿病（DM）患者高血糖诱导的肾毒性。我们回顾了有关2型糖尿病中遗传学与糖尿病肾病之间关系的现有知识状况。然而，结果尚无定论，糖尿病肾病的遗传决定因素尚未完全明确。此外，2型糖尿病肾病的遗传背景被认为比1型糖尿病更为复杂。最近的研究表明，炎症是2型糖尿病及其并发症的一个重要组成部分。我们推测，在高糖环境中全身和/或肾内炎症增加在2型糖尿病患者肾病的发病机制中起重要作用。为了研究炎症对糖尿病肾病的影响，我们研究了2型糖尿病患者中编码炎性细胞因子和趋化因子的基因中的几种多态性。其中，白细胞介素-1β（IL-1β）基因中的-511 C/T、白细胞介素-1受体拮抗剂（IL-1Ra）中的串联重复、肿瘤坏死因子-α（TNF-α）基因中的-308 G/A与肾衰竭风险增加显著相关。此外，其中一些与先前在NCBI或基于西方人群的文献中报道的结果明显不同。我们的结果表明，炎症可能在2型糖尿病肾病中起致病作用。更好地了解糖尿病肾病的遗传易感性因素不仅有助于识别有风险的糖尿病患者，也有助于揭示糖尿病肾病的发病机制。
