Urinary MicroRNA Profiling Predicts the Development of Microalbuminuria in Patients with Type 1 Diabetes.
Urinary MicroRNA Profiling Predicts the Development of Microalbuminuria in Patients with Type 1 Diabetes.
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DOI：
10.3390/jcm4071498
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发表时间：
2015-07-17
影响因子：
3.9
通讯作者：
Johnson JP
中科院分区：
文献类型：
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作者：
Argyropoulos C;Wang K;Bernardo J;Ellis D;Orchard T;Galas D;Johnson JP
微量白蛋白尿是 1 型糖尿病患者糖尿病肾病的最早临床标志物，但其对疾病早期组织学表现缺乏敏感性和特异性。近年来，microRNA 已成为糖尿病并发症发病机制中的潜在介质，这表明其在早期疾病的诊断中可能发挥作用。我们使用定量聚合酶链反应 (qPCR) 来评估未发展为肾病的患者 (n = 10) 与随后发展为微量白蛋白尿的患者 (n = 17) 的正常白蛋白尿中 723 种独特 microRNA 的表达谱。 18 个 microRNA 与微量白蛋白尿的后续发展密切相关，而 15 个 microRNA 表现出与性别相关的表达差异。这些 microRNA 的预测靶标映射到已知参与糖尿病肾病发病机制和进展的生物途径。 microRNA 特征（miR-105-3p、miR-1972、miR-28-3p、miR-30b-3p、miR-363-3p、miR-424-5p、miR-486-5p、miR-495、miR-548o-3p 以及女性 miR-192-5p、miR-720）实现了较高的内部效度（交叉验证）错误分类率为 11.1%），以预测该数据集中微量白蛋白尿的未来发展。通过肾脏相关靶标的数量对 microRNA 测量值进行加权可以改善 miRNA 特征的预后性能（交叉验证的错误分类率为 7.4%）。未来的研究需要在更大的队列中证实这些早期观察结果。
Microalbuminuria provides the earliest clinical marker of diabetic nephropathy among patients with Type 1 diabetes, yet it lacks sensitivity and specificity for early histological manifestations of disease. In recent years microRNAs have emerged as potential mediators in the pathogenesis of diabetes complications, suggesting a possible role in the diagnosis of early stage disease. We used quantiative polymerase chain reaction (qPCR) to evaluate the expression profile of 723 unique microRNAs in the normoalbuminuric urine of patients who did not develop nephropathy (n = 10) relative to patients who subsequently developed microalbuminuria (n = 17). Eighteen microRNAs were strongly associated with the subsequent development of microalbuminuria, while 15 microRNAs exhibited gender-related differences in expression. The predicted targets of these microRNAs map to biological pathways known to be involved in the pathogenesis and progression of diabetic renal disease. A microRNA signature (miR-105-3p, miR-1972, miR-28-3p, miR-30b-3p, miR-363-3p, miR-424-5p, miR-486-5p, miR-495, miR-548o-3p and for women miR-192-5p, miR-720) achieved high internal validity (cross-validated misclassification rate of 11.1%) for the future development of microalbuminuria in this dataset. Weighting microRNA measurements by their number of kidney-relevant targets improved the prognostic performance of the miRNA signature (cross-validated misclassification rate of 7.4%). Future studies are needed to corroborate these early observations in larger cohorts.