Identification of potential crucial genes and therapeutic targets for epilepsy

Abstract

Background: Epilepsy, a central neurological disorder, has a complex genetic architecture. There is some evidence suggesting that genetic factors play a role in both the occurrence of epilepsy and its treatment. However, the genetic determinants of epilepsy are largely unknown. This study aimed to identify potential therapeutic targets for epilepsy.

Methods: Differentially expressed genes (DEGs) were extracted from the expression profiles of GSE44031 and GSE1834. Gene co-expression analysis was used to confirm the regulatory relationship between newly discovered epilepsy candidate genes and known epilepsy genes. Expression quantitative trait loci analysis was conducted to determine if epilepsy risk single-nucleotide polymorphisms regulate DEGs' expression in human brain tissue. Finally, protein-protein interaction analysis and drug-gene interaction analysis were performed to assess the role of DEGs in epilepsy treatment.

Results: The study found that the protein tyrosine phosphatase receptor-type O gene (PTPRO) and the growth arrest and DNA damage inducible alpha gene (GADD45A) were significantly upregulated in epileptic rats compared to controls in both datasets. Gene co-expression analysis revealed that PTPRO was co-expressed with RBP4, NDN, PAK3, FOXG1, IDS, and IDS, and GADD45A was co-expressed with LRRK2 in human brain tissue. Expression quantitative trait loci analysis suggested that epilepsy risk single-nucleotide polymorphisms could be responsible for the altered PTPRO and GADD45A expression in human brain tissue. Moreover, the protein encoded by GADD45A had a direct interaction with approved antiepileptic drug targets, and GADD45A interacts with genistein and cisplatin.

Conclusions: The results of this study highlight PTPRO and GADD45A as potential genes for the diagnosis and treatment of epilepsy.

Keywords: Epilepsy; GADD45A; Gene; PTPRO; Target.

Fig. 1

DEGs were identified from GSE44031 and GSE1834 gene expression profiling datasets based on adjusted p value < 0.05 and |logfold change|≥ 1. The two datasets share 5 overlapping DEGs

Fig. 2

The volcano plot illustrates DEGs. The volcano plot illustrates DEGs between epilepsy and control after analysis of the GSE44031 gene expression profiling datasets

Fig. 3

Analysis of gene co-expression in human brain. PTPRO was co-expressed with RBP4, NDN, PAK3, FOXG1, IDS, and IDS, and GADD45A was co-expressed with LRRK2 in human brain tissue

Fig. 4

The PPI network of PTPRO and GADD45A and the genes whose encoded protein targeted by antiepileptic drugs. The proteins connected by the red line mean that they have direct interactions