The decorin gene 179 allelic variant is associated with a slower progression of renal disease in patients with type 1 diabetes
The decorin gene 179 allelic variant is associated with a slower progression of renal disease in patients with type 1 diabetes
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DOI：
10.1159/000064470
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发表时间：
2002-09-01
期刊：
影响因子：
2.5
通讯作者：
Viberti, GC
中科院分区：
文献类型：
--
作者：
De Cosmo, S;Tassi, V;Viberti, GC
背景遗传因素可能影响1型糖尿病肾病进展速率的变异性。在糖尿病中，进行性系膜基质扩张和肾小球硬化在很大程度上是由tgf - β 1介导的。Decorin是一种蛋白聚糖，是细胞外基质的组成部分，调节tgf - β 1的活性和表达。我们研究了Decorin基因179/183/185多态性与糖尿病肾病进展之间的关系。方法：从175名欧洲糖尿病肾病患者的队列中，我们研究了79名患者，这些患者被选中是因为他们有至少2年的随访（平均6.5年；范围：2.5-15年），并在5次或5次以上的情况下定期测量血清肌酐。从血清肌酐浓度计算的肌酐清除率（CrCl）被用作衍生肾小球滤过率（dGFR）的测量。所有患者均接受抗高血压治疗。结果：整个队列dGFR下降率[中位数（范围）]4.6(-3.8至18)ml/min/年。无185等位基因患者。179/183和179/179基因型患者（n = 14）与Decorin 183/183基因型患者（n = 65）相比，GFR下降速度较慢[2.1 (0.06-11.7)ml/min/年][5.6 (-3.8 - 18)ml/min/年]；P < 0.001]。此外，在考虑个体数据时，携带179等位基因的患者出现缓慢进展（即GFR降至中位数以下）的概率高出3.0倍（95%Cl: 1.8-4.2）。这种差异不能用疾病持续时间、抗高血压治疗类型和持续时间、白蛋白排泄率、血糖或血压控制的差异来解释。在多因素logistic分析中，白蛋白排泄率（p < 0.001）、平均动脉压（p = 0.07）和Decorin基因多态性（p = 0.036）与dGFR下降率独立相关，但与HbA1c无关。结论：Decorin基因179等位基因变异与1型糖尿病合并蛋白尿并接受降压治疗的患者DN进展缓慢有关。版权所有(C) 2002 S. Karger AG，巴塞尔。
Background genetic factors may influence the variability in the rate of progression of kidney disease in type I diabetes. In diabetes, progressive mesangial matrix expansion and glomerular sclerosis are, to a large extent, mediated by TGF-beta1. Decorin, a proteoglycan which is a component of the extracellular matrix, regulates TGF-beta1 activity and expression. We have examined the relationship between the 179/183/185 polymorphism of the Decorin gene and the progression of diabetic nephropathy. Methods: From a cohort of 175 European patients with diabetic nephropathy, we studied 79 patients who were selected because they had a follow-up of at least 2 years (average 6.5 years; range: 2.5-15 years), and regular measurements of serum creatinine on 5 or more occasions. Creatinine clearance (CrCl) calculated from serum creatinine concentration was used as a measure of derived glomerular filtration rate (dGFR). All patients were on anti hypertensive therapy. Results: The rate of dGFR decline in the whole cohort was [median (range)] 4.6 (-3.8 to 18) ml/min/year. No patient with 185 allele was found. Patients with 179/183 and 179/179 genotype (n = 14), who were considered together and named 179 carriers, had a slower rate of GFR decline [2.1 (0.06-11.7) ml/min/year] as compared to patients with Decorin 183/183 genotype (n = 65) [5.6 (-3.8 to 18) ml/min/year; p < 0.001]. In addition, when considering individual data, patients carrying the 179 allele had a 3.0 (95%Cl: 1.8-4.2)-fold higher probability to be slow progressors (i.e. GFR decline below the median). This difference could not be accounted for by differences in duration of disease, type and duration of anti hypertensive therapy, albumin excretion rate, blood glucose or blood pressure control. In a multivariate logistic analysis albumin excretion rate (p < 0.001), mean arterial pressure (p = 0.07) and Decorin gene polymorphism (p = 0.036), but not HbA1c, were independently correlated with the rate of dGFR fall. Conclusion: The 179 allele variant of the Decorin gene is related to a slower progression of DN in type 1 diabetic patients with albuminuria and receiving antihypertensive therapy. Copyright (C) 2002 S. Karger AG, Basel.