mRNA blood expression patterns in new-onset idiopathic pediatric epilepsy

Epilepsia. 2013 Feb;54(2):272-9. doi: 10.1111/epi.12016. Epub 2012 Nov 21.

Abstract

Purpose: Determine if blood messenger RNA (mRNA) expression patterns in children with newly diagnosed untreated idiopathic epilepsy are different from those in healthy controls. Determine the differential expression patterns between epilepsy patients with generalized onset or partial onset seizures compared to healthy controls.

Methods: Whole blood was obtained from otherwise healthy pediatric patients with newly diagnosed untreated idiopathic epilepsy along with healthy pediatric controls. mRNA was isolated and hybridized to Affymetrix HGU 133 2.0+ microarrays. Analysis was performed using Genespring. Differentially expressed gene lists resulted from comparison of (1) epilepsy and control groups and (2) seizure type subgroups with controls. Tissue expression and gene ontology analysis was performed using DAVID.

Key findings: Thirty-seven epilepsy patients and 28 controls were included. Overall, 575 genes were differentially expressed in subjects with epilepsy compared to controls. The generalized seizure subgroup versus control (GvC) gene list and the partial seizure subgroup versus control (PvC) gene list were different (p < 0.05). Tissue expression analysis identified almost half of the genes in GvC and PvC as brain based. Functional group analysis identified several biologically relevant pathways. In GvC, these included mitochondria and lymphocyte activation. In PvC, we identified apoptosis, inflammatory defense, and cell motion pathways.

Significance: A unique, biologically meaningful mRNA expression pattern is detectable in whole blood of pediatric subjects with new-onset and untreated epilepsy. This analysis finds many similar pathways to those identified in brain studies examining lesional intractable epilepsy. Blood mRNA expression patterns show promise as a target for biomarker development in pediatric epilepsy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Cohort Studies
  • Epilepsies, Partial / genetics
  • Epilepsy / blood
  • Epilepsy / genetics*
  • Epilepsy, Generalized / genetics
  • Female
  • Gene Expression Regulation
  • Genetic Markers / genetics
  • Humans
  • Lymphocyte Activation / genetics
  • Male
  • Microarray Analysis
  • Mitochondria / metabolism
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / blood*

Substances

  • Genetic Markers
  • RNA, Messenger
  • RNA