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Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Diagnosis and Drug Prediction of Parkinson's Disease Based on Immune-Related Genes
Jinglei Bao1, Wansheng Chang1, Yanjun Zhao2
1Department of Internal Neurology, The Second People's Hospital of Liao Cheng, Shandong Province, China.
Abstract:
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Immune mechanisms play an important role in the development of PD. The purpose of this study was to identify potential differentially expressed immune-related genes (IRGs), signaling pathways, and drugs in PD, which may provide new diagnostic markers and therapeutic targets for PD. Differentially expressed genes (DEGs) and IRGs were respectively obtained from the Gene Expression Omnibus (GEO) dataset and the ImmPort database. Weighted gene co-expression network analysis (WGCNA) was utilized to further identify hub IRGs. Core IRGs were obtained by intersection of DEGs and hub genes in the module of WGCNA, followed by construction of diagnostic models and regulation network establishment of long non-coding RNAs (lncRNAs)-miRNAs-diagnostic IRGs. Analysis of functional enrichment and protein-protein interaction (PPI) network and identification of related drugs of DEGs was performed. LILRB3 and CSF3R were identified as potential diagnostic markers for PD. Two regulatory pairs were identified based on LILRB3 and CSF3R, including XIST-hsa-miR-214-3p/hsa-miR-761-LILRB3 and XIST-hsa-miR-485-5p/hsa-miR-654-5p-CSF3R. LEP and IL1A were drug targets of Olanzapine. MMP9 and HSP90AB1 were drug targets of Bevacizumab. In addition, LEP and MMP9 were respectively drug targets of Lovastatin and Celecoxib. Herpes simplex infection (involved TNFRSF1A) and cytokine-cytokine receptor interaction (involved CSF3R, LEP, and IL1A) were the most remarkably enriched signaling pathways of DEGs. Identified IRGs and related signaling pathways may play critical roles in the development of PD. Additionally, LILRB3 and CSF3R can be considered as potential immune-related diagnostic markers for PD. LEP, IL1A, MMP9, and HSP90AB1 may be regarded as immune-related therapeutic targets for PD.
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