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利用靶向蛋白质组学芯片探索糖尿病发病的病理生理途径-马尔默预防项目。

Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes- The Malmö Preventive Project.

机构信息

Department of Clinical Sciences, Lund University, Clinical Research Center, Malmö, Sweden.

Department of Cardiology, Skåne University Hospital Malmö, Malmö, Sweden.

出版信息

Sci Rep. 2019 Jan 22;9(1):272. doi: 10.1038/s41598-018-36512-y.

Abstract

Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.

摘要

多重蛋白质组学平台为研究多种蛋白质与疾病(如糖尿病)之间的关联提供了极好的工具,这些关联可能具有预后、诊断和治疗意义。在这项研究中,我们的目的是通过检测 92 种蛋白质及其与人群队列中(146 例糖尿病与 880 例对照)发病糖尿病的关联,来探索新的病理生理途径,该队列随访了 8 年以上。在调整了传统危险因素后,我们确定了 7 种与发病糖尿病相关的蛋白质。其中 4 种蛋白质(清道夫受体富含胱氨酸域蛋白 1 型 M130、脂肪酸结合蛋白 4、纤溶酶原激活物抑制剂 1 和胰岛素样生长因子结合蛋白 2)与发病糖尿病的先前已建立的关联有关,而 3 种蛋白质(组织蛋白酶 D、半乳糖凝集素-4、对氧磷酶 3)与发病糖尿病具有新的关联。半乳糖凝集素-4 与糖尿病的发病风险增加有关,而对氧磷酶 3 与糖尿病的发病风险降低有关,在调整血糖后,这两种蛋白质与发病糖尿病仍有显著关联,这表明它们与糖尿病之间存在与血糖无关的关联。

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