CONTEXT Islet autoantibodies (IAbs) are currently the most reliable indicators of islet autoimmunity. However, IAbs do not fully meet the need for the prediction and intervention of type 1 diabetes (T1D). Serological proteins should be great sources for biomarkers. OBJECTIVE This work aimed to identify new proteomic biomarkers with the technology of an expression-based genome-wide association study (eGWAS) in children newly diagnosed with T1D. METHODS In an attempt to identify additional biomarkers, we performed an eGWAS using microarray data from 169 arrays of the pancreatic islets of T1D rodents (78 T1D cases and 91 controls). We ranked all 16 099 protein-coding genes by the likelihood of differential expression in the pancreatic islets. Our top 20 secreted proteins were screened in 170 children including 100 newly diagnosed T1D, and 50 type 2 diabetes (T2D) and 20 age-matched healthy children. With 6 proteins showing significance, we further conducted a validation study using the second independent set of 400 samples from children including 200 newly diagnosed with T1D, 100 T2D, and 100 age-matched controls. RESULTS We identified 2 serum proteins that were significantly changed in T1D vs both control and T2D, and 5 serum proteins were significantly changed both in T1D and T2D vs control. Serum osteopontin (OPN) levels were uniquely higher in T1D (T1D vs controls, P = 1.29E-13 ~ 9.38E-7, T1D vs T2D, P = 2.65E-8 ~ 1.58E-7) with no difference between T2D and healthy control individuals. Serum interleukin 1 receptor antagonist (IL-1RA) levels were lower in T1D compared both with T2D (P = 3.36E-9~0.0236) and healthy participants (P = 1.09E-79 ~ 2.00E-12). CONCLUSION Our results suggest that OPN and IL1-RA could be candidates for useful biomarkers for T1D in children.

中文翻译：

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基于表达的全基因组关联研究将 OPN 和 IL1-RA 与新诊断的儿童 1 型糖尿病联系起来。

背景胰岛自身抗体 (IAb) 是目前最可靠的胰岛自身免疫指标。然而，IAb 并不能完全满足 1 型糖尿病（T1D）预测和干预的需要。血清蛋白应该是生物标志物的重要来源。目的 这项工作旨在通过基于表达的全基因组关联研究 (eGWAS) 技术在新诊断为 T1D 的儿童中识别新的蛋白质组生物标志物。方法 为了识别其他生物标志物，我们使用来自 169 个 T1D 啮齿动物胰岛阵列（78 个 T1D 病例和 91 个对照）的微阵列数据进行了 eGWAS。我们根据胰岛中差异表达的可能性对所有 16 099 个蛋白质编码基因进行了排序。我们在 170 名儿童中筛选了前 20 种分泌蛋白，其中包括 100 名新诊断的 T1D，50 名 2 型糖尿病 (T2D) 患者和 20 名年龄匹配的健康儿童。由于 6 种蛋白质显示出显着性，我们进一步使用第二组独立的 400 个儿童样本进行了验证研究，其中包括 200 个新诊断为 T1D 的儿童、100 个 T2D 和 100 个年龄匹配的对照。结果 我们确定了 2 种血清蛋白在 T1D 中与对照和 T2D 相比有显着变化，5 种血清蛋白在 T1D 和 T2D 中与对照相比有显着变化。血清骨桥蛋白 (OPN) 水平在 T1D 中特别高（T1D 与对照组相比，P = 1.29E-13 ~ 9.38E-7，T1D 与 T2D 相比，P = 2.65E-8 ~ 1.58E-7），T2D 和 T2D 之间没有差异健康对照个体。与 T2D (P = 3.36E-9~0.0236) 和健康参与者 (P = 1.09E-79 ~ 2.00E-12) 相比，T1D 患者血清白细胞介素 1 受体拮抗剂 (IL-1RA) 水平较低。