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 ai...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-024-01643-8 |
| _version_ | 1797355945788964864 |
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| author | Shitao Wang Zhenrong Xie Tian Jun Xuelu Ma Mengen Zhang Feng Rao Hui Xu Jinghong Lu Xiangqian Ding Zongyou Li |
| author_facet | Shitao Wang Zhenrong Xie Tian Jun Xuelu Ma Mengen Zhang Feng Rao Hui Xu Jinghong Lu Xiangqian Ding Zongyou Li |
| author_sort | Shitao Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T14:18:29Z |
| format | Article |
| id | doaj.art-bf4799d276434c9186c5dfc5627b0bfd |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-08T14:18:29Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-bf4799d276434c9186c5dfc5627b0bfd2024-01-14T12:16:31ZengBMCEuropean Journal of Medical Research2047-783X2024-01-012911710.1186/s40001-024-01643-8Identification of potential crucial genes and therapeutic targets for epilepsyShitao Wang0Zhenrong Xie1Tian Jun2Xuelu Ma3Mengen Zhang4Feng Rao5Hui Xu6Jinghong Lu7Xiangqian Ding8Zongyou Li9Department of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityThe Medical Biobank, First Affiliated Hospital of Kunming Medical UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityDepartment of Neurosurgery, Qilu Hospital of Shandong UniversityDepartment of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical UniversityAbstract 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.https://doi.org/10.1186/s40001-024-01643-8GeneEpilepsyPTPROGADD45ATarget |
| spellingShingle | Shitao Wang Zhenrong Xie Tian Jun Xuelu Ma Mengen Zhang Feng Rao Hui Xu Jinghong Lu Xiangqian Ding Zongyou Li Identification of potential crucial genes and therapeutic targets for epilepsy European Journal of Medical Research Gene Epilepsy PTPRO GADD45A Target |
| title | Identification of potential crucial genes and therapeutic targets for epilepsy |
| title_full | Identification of potential crucial genes and therapeutic targets for epilepsy |
| title_fullStr | Identification of potential crucial genes and therapeutic targets for epilepsy |
| title_full_unstemmed | Identification of potential crucial genes and therapeutic targets for epilepsy |
| title_short | Identification of potential crucial genes and therapeutic targets for epilepsy |
| title_sort | identification of potential crucial genes and therapeutic targets for epilepsy |
| topic | Gene Epilepsy PTPRO GADD45A Target |
| url | https://doi.org/10.1186/s40001-024-01643-8 |
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