Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder

Kaminski, Valéria de Lima; Kulmann-Leal, Bruna; Tyska-Nunes, Guilherme Luís; Beltrame, Brenda Pedron; Riesgo, Rudimar dos Santos; Schüler-Faccini, Lavinia; Roman, Tatiana; Schuch, Jaqueline Bohrer; Chies, José Artur Bogo

doi:10.1016/j.jneuroim.2023.578132

Cited by 1 publication

(1 citation statement)

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“…Therefore, the results of the PPI networks and drug–gene interaction further underscore the significant role of GADD45A in epilepsy therapy. While recent studies have discovered new epilepsy-related genes [ 46 , 47 ], our study not only identified new epilepsy-related genes but also explored the potential mechanisms of these new genes in the pathogenesis and treatment of epilepsy, which could be more conducive to the transformation of clinical application.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential crucial genes and therapeutic targets for epilepsy

Wang,

Xie,

Jun

et al. 2024

Eur J Med Res

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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.

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Section: Discussionmentioning

confidence: 99%