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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2024

Open Access 01-12-2024 | Epilepsy | Research

Identification of potential crucial genes and therapeutic targets for epilepsy

Authors: Shitao Wang, Zhenrong Xie, Tian Jun, Xuelu Ma, Mengen Zhang, Feng Rao, Hui Xu, Jinghong Lu, Xiangqian Ding, Zongyou Li

Published in: European Journal of Medical Research | Issue 1/2024

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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.
Appendix
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Metadata
Title
Identification of potential crucial genes and therapeutic targets for epilepsy
Authors
Shitao Wang
Zhenrong Xie
Tian Jun
Xuelu Ma
Mengen Zhang
Feng Rao
Hui Xu
Jinghong Lu
Xiangqian Ding
Zongyou Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2024
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-024-01643-8

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