Identification of Shared Pathogenetic Genes in Parkinson’s Disease and Type 2 Diabetes

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Increasing evidence suggests that PD patients have alterations in glucose metabolism and that type 2 diabetes (T2D) is a risk factor for PD. Although extensive literature has shown that there is a close linkage between PD and T2D, the molecular and genetic mechanisms of these two diseases are still unclear. Object: The aim of this study was to explore the shared pathogenetic genes in PD and T2D. Method: We downloaded microarray data for PD and T2D from the Gene Expression Omnibus (GEO) database. The RNA microarray data of human postmortem substantia nigra samples were accessed from the GSE49036, GSE20141 and GSE7621 datasets. The RNA microarray data of human pancreatic islet samples were from the GSE76896 dataset. The differentially expressed genes between the PD/control and T2D/control groups were analyzed. Gene coexpression modules related to PD and T2D were constructed by weighted gene coexpression network analysis (WGCNA). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the common genes between the PD and T2D key modules. Finally, through protein‒protein interaction (PPI) network analysis, four shared pathogenetic genes were identified. Result: There were 348 downregulated differentially expressed genes and 221 upregulated differentially expressed genes between PD patients and healthy controls. There were 218 downregulated differentially expressed genes and 65 upregulated differentially expressed genes between T2D patients and healthy controls. Thirty-six common differentially expressed genes with consistent fold change directions were obtained from the overlapping differentially expressed genes between the PD and T2D datasets. In the PD datasets, the turquoise module was the key module related to the pathogenesis of PD and included 3735 genes. In the T2D dataset, the turquoise module was the most significant module related to the pathogenesis of T2D and included 790 genes. The common genes between the PD and T2D key modules were primarily enriched in synaptic transmission and insulin signaling. After the construction of the PPI network, we identified four shared pathogenetic genes, namely, TAGLN3, STMN2, SYT4 and GAP43. Conclusion: In conclusion, TAGLN3, STMN2, SYT4 and GAP43 were the shared pathogenetic genes of PD and T2D, which might provide new therapeutic targets for PD and T2D.