C-106T polymorphism in promoter of aldose reductase gene is a risk factor for diabetic nephropathy in type 2 diabetes patients with poor glycaemic control
C-106T polymorphism in promoter of aldose reductase gene is a risk factor for diabetic nephropathy in type 2 diabetes patients with poor glycaemic control
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DOI：
10.1159/000083209
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Zukowska-Szczechowska, E
中科院分区：
文献类型：
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作者：
Gosek, K;Moczulski, D;Zukowska-Szczechowska, E
背景资料：长期以来，通过多元醇途径的过度通量被认为参与糖尿病微血管并发症的发病机制。醛糖还原酶（AR）是催化葡萄糖还原为山梨醇的第一个酶，也是限速酶。AR基因启动子区C-106 T多态性是一种常见的基因多态性，它可能改变AR基因的表达。该研究的目的是检查C-106 T多态性是否与糖尿病肾病相关。材料和方法：我们收集了444例2型糖尿病患者，并根据肾脏状态将其分为三组：正常白蛋白尿162例，微量白蛋白尿153例和持续性蛋白尿129例。采用基于PCR的RFLP方案对每个受试者进行C-106多态性基因分型。结果：当对整个研究人群进行分析时，没有观察到研究组之间的基因型频率失真。当我们根据HbA 1c对研究人群进行分层时，我们发现在HbA 1c ≥ 9%（中位数）的患者中，糖尿病肾病（蛋白尿和微量白蛋白尿）患者的CT和TT基因型比正常白蛋白尿患者更常见（OR 2.04，95%CI 1.12 - 3.74）。结论：AR基因C-106 T多态性是血糖控制不佳的2型糖尿病患者发生糖尿病肾病的危险因素。版权所有（C）2005 S. Karger AG，巴塞尔。
Background: Excessive flux through the polyol pathway has long been thought to be involved in the pathogenesis of diabetic microvascular complications. Aldose reductase (AR) is the first and rate-limiting enzyme in the pathway that catalyses the reduction of glucose to sorbitol. A frequent C-106T polymorphism in the promoter of the AR gene has been described, which may change the expression of the gene. The aim of the study was to examine if the C-106T polymorphism was associated with diabetic nephropathy. Material and Methods: We collected 444 patients with type 2 diabetes and divided them into three groups according to the renal status: 162 patients with normoalbuminuria, 153 with microalbuminuria and 129 with persistent proteinuria. Each subject was genotyped for the C-106 polymorphism using the PCR-based RFLP protocol. Results: When the whole study population was analysed, no distortion in the genotype frequency among the study groups was observed. When we stratified the study population by HbA1c we found that in patients with HbA1c greater than or equal to 9% (median) the CT and TT genotypes were more frequent in patients with diabetic nephropathy ( proteinuria and microalbuminuria) than those with normoalbuminuria (OR 2.04, 95% CI 1.12 - 3.74). Conclusion: The C-106T polymorphism in the AR gene is a risk factor for development of diabetic nephropathy in type 2 diabetes in patients with poor glycaemic control. Copyright (C) 2005 S. Karger AG, Basel.