公开(公告)号：US09970056B2

公开(公告)日：2018-05-15

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.