Bioinformatic Identification of Risk Factors from an Immunological Viewpoint in Idiopathic Parkinson’s Disease

Background: In the present study, we focused on uncovering stable genetic alterations associated with idiopathic Parkinson’s disease (IPD) in blood samples. We aimed to identify factors that connect IPD to the peripheral immune system, thereby deepening our understanding of the pathophysiology of this disease.

Methods: A gene expression microarray dataset (GSE99039) was selected from the National Center for Biotechnology Information Gene Expression Omnibus database to screen for differentially expressed genes (DEGs). Subsequent analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. A protein–protein interaction network was then constructed to identify hub genes within these DEGs. Additionally, we used a verification dataset (GSE160299) to test the consistency of the expression level changes of the hub genes.

Results: We identified 277 DEGs, comprising 270 downregulated genes and 7 upregulated genes. The functional enrichment results revealed a close association between IPD and changes in peripheral immune status. Five hub genes—HLA-F, HLA-E, KIR3DL2, KIR3DL1, and TYROBP—were identified, and the expression level changes remained stable in the verification set.

Conclusions: Our findings help to clarify the regulatory pathways that connect peripheral immunity to IPD pathogenesis. We identified five key hub genes in the blood as IPD-related factors; all five genes were also significantly altered in an independent clinical dataset.