Pharmacogenomic Analysis of Medial Temporal Lobe Epilepsy with Hippocampal Sclerosis in Humans and Animal Models

Abstract Background Epilepsy is a neurological disorder caused by abnormal brain discharges. In recent years, genome-wide expression studies (GES) have been conducted using human patient samples and experimental models of epilepsy. Numerous molecular targets for epileptogenesis and treatment have been identified. However, there is still an urgent need to identify new biomarkers for epilepsy. Methods We performed a meta-analysis and convergence analysis of GES available from human samples and mouse and rat models to identify differentially expressed genes. Functional and pathway enrichment analysis of differentially expressed genes was performed using Sangerbox 3.0. Protein–protein interaction networks were mapped using STRING and subsequently visualized using Cytoscape. Disease gene–drug interactions were explored using the Comparative Toxicology Database and the Drug Gene Interaction Database. Results The ten most highly differentially expressed genes were, LRRTM1, STX1A, SNAP25, SYNPR, STXBP1, NRXN1, CPLX1, SYT4, SYT13 and GABRG2, which were supported by multi-lineage genomic evidence. A functional enrichment analysis identified several important classifications, including regulation of neuronal differentiation and regulation of vesicle-mediated transport. Potential druggable genes were also identified (e.g., LRRTM1, GABRG2, CYP4X1, CHGB and TMEM130). Conclusions We performed a meta-analysis and convergence analysis of GES from human samples and multiple animal models of epileptogenesis by integrating the results of several studies. We identified the top ten candidate genes and pathways for epileptogenesis. Among them, LRRTM1 and GABRG2 have been validated to have high druggable value. The other eight genes require further study to explore their potential as therapeutic targets in medial temporal lobe epilepsy with hippocampal sclerosis.