Development of microarray-based biomarkers for diabetes melitus

基于微阵列的糖尿病生物标志物的开发

• 批准号: 7272805
• 负责人: JIN-XIONG SHE
• 金额: $ 35.9万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7272805
• 关键词: Antigens; Autoantibodies; Biological Assay; Biological Markers; Clinical; Cross-Sectional Studies; Data Set; Development; Diabetes Mellitus; Disease; Disease Marker; Economics; Environment; Gene Expression; Genes; Genomics; Immune system; Individual; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans; Laboratories; Measurement; Modeling; Molecular; Molecular Profiling; Patients; Peripheral Blood Lymphocyte; Phase; Population; Rate; Research Design; Research Personnel; Risk Assessment; Screening procedure; Series; Staging; Susceptibility Gene; T-Lymphocyte; Testing; base; disorder prevention; novel; programs; prospective; tool

DESCRIPTION (provided by applicant): Type 1 diabetes (T1D) results from poorly defined interactions between susceptibility genes, the environment, and the immune system. The long presymptomatic period, during which a series of islet-cell antigen-specific autoantibodies (Ab), activated T-cells and other molecular changes arise, provides an opportunity for disease prevention. Accurate risk assessment is vital for disease prevention so that therapy can be given to those individuals who are very likely to develop the disease. Despite the identification of several useful disease markers such as autoantibodies, there is still an urgent need for more specific and earlier T1D markers. Unfortunately, progress has been very slow until the recent developments of novel genomic tools. By expression profiling of peripheral blood lymphocytes, we identified several hundred genes that are differentially expressed in Ab negative (AbN) controls versus T1D patients and Ab positive (AbP) subjects. Using multivariate models of gene expression, we identified two AbP subsets who have different progression rates to T1D, suggesting that expression profiling may be very powerful T1D markers. In the R21 phase, we will carry out a cross-sectional study to confirm our preliminary findings and to develop novel biomarkers for accurate risk assessment for the transition from AbP to T1D as well as from AbN to AbP stages. Once the feasibility is demonstrated in the R21 phase, we will validate, in the R33 phase, the novel biomarkers in a prospective data set. We will also develop and validate highly reproducible and economic assays for efficient measurement of these biomarkers and the new assays will be tested in two large population screening programs (PANDA and DAISY) that have been underway in the investigators' laboratory. These step-wise studies are designed to develop and validate novel biomarkers and bring them to clinical use.

描述（由申请人提供）： 1型糖尿病（T1D）是由易感基因、环境和免疫系统之间的相互作用引起的。在此期间，一系列胰岛细胞抗原特异性自身抗体（Ab），活化的T细胞和其他分子变化的出现，为疾病预防提供了机会。准确的风险评估对于疾病预防至关重要，以便能够对那些很可能患上这种疾病的人进行治疗。尽管鉴定了几种有用的疾病标志物，如自身抗体，但仍然迫切需要更特异和更早的T1D标志物。不幸的是，直到最近新的基因组工具的发展，进展一直非常缓慢。通过对外周血淋巴细胞的表达谱分析，我们鉴定了数百个在Ab阴性（AbN）对照与T1D患者和Ab阳性（AbP）受试者中差异表达的基因。使用多变量模型的基因表达，我们确定了两个AbP子集谁有不同的进展速度T1D，表明表达谱可能是非常强大的T1D标记。在R21阶段，我们将进行一项横断面研究，以证实我们的初步发现，并开发新的生物标志物，用于准确评估从AbP过渡到T1D以及从AbN过渡到AbP阶段的风险。一旦在R21阶段证明了可行性，我们将在R33阶段验证前瞻性数据集中的新型生物标志物。我们还将开发和验证用于有效测量这些生物标志物的高度可重复和经济的检测方法，新的检测方法将在研究者实验室正在进行的两个大型人群筛查项目（PANDA和DAISY）中进行测试。这些逐步研究旨在开发和验证新的生物标志物，并将其用于临床。