Integrative analysis of gene expression associated with epilepsy in human epilepsy and animal models

Abstract

Epilepsy is a severe neuropsychiatric disorder, the cause of which remains to be elucidated. Genome-wide association studies, DNA microarrays and proteomes have been widely applied to identify the candidate genes involved in epileptogenesis, and integrative analyses are often capable of extracting more detailed biological information from the data. In the present study, a total number of 1,065 genes in different animal models were collected to construct an epilepsy candidate gene database. Further analyses suggested that the response to organic substances, the intracellular signaling cascade and neurological system processes were significantly enriched biological processes, and the mitogen-activated protein kinase pathway was identified as a putative epileptogenic signaling pathway. In addition, the five key genes, growth factor receptor bound 2, amyloid β (A4) precursor protein, transforming growth factor-β, vascular endothelial growth factor and cyclin-dependent kinase inhibitor 1, were identified as being critical as central nodes in the protein networks. Reverse transcription-quantitative polymerase chain reaction analysis revealed that these genes were all upregulated at the mRNA level in the epileptic loci compared with the resection margin of tissue samples from the same patients diagnosed with epilepsy. The data mining performed in the present study thus was shown to be a useful tool, which may contribute to obtaining further information on epileptic disorders and delineating the molecular mechanism of the associated genes.