公开(公告)号：US20160244833A1

公开(公告)日：2016-08-25

申请号：US14870960

申请日：2015-09-30

Applicant: Rosalind Franklin University of Medicine and Science

Inventor： Judith Ann POTASHKIN ,  Jose Alfredo SANTIAGO

IPC: C12Q1/68

CPC classification number: C12Q1/6883 ,  C12Q2600/158

Abstract: Network-based meta-analysis of four independent microarray studies identified the hepatocyte nuclear factor (HNF4A), a transcription factor associated with gluconeogenesis and diabetes, as a central regulatory hub gene upregulated in blood of PD patients. In parallel, the polypyrimidine tract binding protein 1 (PTBP1), involved in the stabilization and mRNA translation of insulin, was identified as the most downregulated gene. Using both markers, PD patients were classified with 90% sensitivity and 80% specificity. Longitudinal performance analysis demonstrated that relative abundance of HNF4A and PTBP1 mRNAs significantly decreased and increased, respectively, in PD patients during 3 years follow up period. The inverse regulation of HNF4A and PTBP1 provides a molecular rationale for the altered insulin signaling observed in PD patients. The longitudinally dynamic biomarkers identified in this study may be useful for monitoring disease-modifying therapies for PD.

Abstract translation: 四个独立的微阵列研究的基于网络的荟萃分析确定了肝细胞核因子（HNF4A），一种与糖异生和糖尿病相关的转录因子，作为PD患者血液中枢调节中枢基因。 同时，涉及胰岛素的稳定和mRNA翻译的聚嘧啶多肽结合蛋白1（PTBP1）被鉴定为最下调的基因。 使用两个标记物，PD患者被分类为90％敏感性和80％特异性。 纵向性能分析表明，3年随访期间，PD患者HNF4A和PTBP1 mRNA的相对丰度分别显着降低和升高。 HNF4A和PTBP1的逆调节为PD患者观察到的改变的胰岛素信号提供了分子依据。 在本研究中鉴定的纵向动态生物标志物可能用于监测PD的疾病修复治疗。

公开(公告)号：US20160244832A1

公开(公告)日：2016-08-25

申请号：US14870931

申请日：2015-09-30

Applicant: Rosalind Franklin University of Medicine and Science

Inventor： Judith Ann POTASHKIN ,  Jose Alfredo SANTIAGO

IPC: C12Q1/68

CPC classification number: C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/158

Abstract: Increasing evidence indicates that Parkinson's disease (PD) and type 2 diabetes (T2DM) share dysregulated molecular networks. 84 genes shared between PD and T2DM were identified from curated disease-gene databases. Nitric oxide biosynthesis, lipid and carbohydrate metabolism, insulin secretion and inflammation were identified as common dysregulated pathways. A network prioritization approach was implemented to rank genes according to their distance to seed genes and their involvement in common biological pathways. This disclosure reinforces the idea that shared molecular networks between PD and T2DM provide an additional source of biologically meaningful biomarkers.

Abstract translation: 越来越多的证据表明帕金森病（PD）和2型糖尿病（T2DM）共享失调的分子网络。 从策划的疾病 - 基因数据库中鉴定了PD和T2DM之间共有84个基因。 一氧化氮生物合成，脂质和碳水化合物代谢，胰岛素分泌和炎症被鉴定为常见的失调途径。 实施了网络优先化方法，以根据其与种子基因的距离及其参与常规生物学途径的方式对基因进行排序。 本公开强调了PD和T2DM之间的共享分子网络提供了生物学有意义的生物标志物的额外来源的想法。