Department of Laboratory Medicine, The Second Hospital of Shandong University, Jinan, 250033 PR China.
J Endocrinol Invest. 2012 Jul;35(7):620-4. doi: 10.1007/BF03345800.
Diabetic nephropathy is a kidney disease or damage that results as a complication of diabetes, especially Type 2 diabetes, while albuminuria is an early marker for diabetic nephropathy as it can predict cardiovascular events and mortality in diabetic patients. A potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. We investigated the associations of the activity-related variants in the TAFI coding gene (505A/G,1040C/T) with the risk of diabetic nephropathy by examining 297samples including 140 health controls and 157 confirmed diabetic nephropathy patients. Diabetic nephropathy grades were further categorized by the urine albumin excretion (UAE)-to-creatinine ratios (ACR). We found little difference that was statistically significant in terms of 505A/G among patients and controls. While at 1040C/T, the detected frequency for the T allele in the group of diabetic nephropathy patients was significantly smaller than that of the control group (15.6% vs 25.7%, respectively; p<0.05). This was due to the relative decrease of T/T homozygotes in the patients (p<0.05, 95% odds ratio 0.28, confidence interval 0.11-0.70). Surprisingly, the difference was only observed with initial diabetic nephropathy stages. This study clearly indicates that, at 1040C/T, the frequency for the T allele is strongly associated with increased risk for diabetic nephropathy in a subset of the general population, implying that the T allele confers protection against the onset of diabetic nephropathy only in homozygosity and may function as a recessive trait.
糖尿病肾病是一种肾脏疾病或损伤，是糖尿病的并发症，尤其是 2 型糖尿病，而白蛋白尿是糖尿病肾病的早期标志物，因为它可以预测糖尿病患者的心血管事件和死亡率。纤溶酶原激活物抑制剂（TAFI）是一种纤维蛋白溶解的有效抑制剂，已从人血浆中分离并鉴定。我们通过检查包括 140 名健康对照者和 157 名确诊的糖尿病肾病患者在内的 297 个样本，研究了 TAFI 编码基因（505A/G，1040C/T）活性相关变异与糖尿病肾病风险之间的关联。糖尿病肾病的分级进一步通过尿白蛋白排泄（UAE）与肌酐比值（ACR）进行分类。我们发现，在患者和对照组之间，505A/G 方面的差异没有统计学意义。而在 1040C/T 中，在糖尿病肾病患者组中 T 等位基因的检出频率明显低于对照组（分别为 15.6%和 25.7%；p<0.05）。这是由于患者中 T/T 纯合子的相对减少（p<0.05，95%置信区间 0.28，0.11-0.70）。令人惊讶的是，这种差异仅在初始糖尿病肾病阶段观察到。这项研究清楚地表明，在 1040C/T 处，T 等位基因的频率与一般人群中某些亚组的糖尿病肾病风险增加密切相关，这意味着 T 等位基因仅在纯合子时对糖尿病肾病的发病具有保护作用，并且可能作为隐性特征起作用。
