title: Cortical gene expression correlates of temporal lobe epileptogenicity.
abstract: BACKGROUND
  Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency.
  
  
  METHODS
  Baseline seizure frequency was used as a clinical measure of epileptogenicity. Twenty-four patients in high or low seizure frequency groups (median seizures/month) underwent anterior temporal lobectomy with amygdalohippocampectomy for intractable TLE. RNA was isolated from the lateral temporal cortex and submitted for expression analysis. Genes significantly associated with baseline seizure frequency on likelihood ratio test were identified based on >0.90 area under the ROC curve, P value of <0.05.
  
  
  RESULTS
  Expression levels of forty genes were significantly associated with baseline seizure frequency. Of the seven most significant, four have been linked to other neurologic diseases. Expression levels associated with high seizure frequency included low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB (POZ) domain containing 11, Thanatos-associated protein domain containing 8 and Heparin sulfate (glucosamine) 3-O-sulfotransferase 3A1.
  
  
  CONCLUSIONS
  This study describes novel associations between forty known genes and a clinical marker of epileptogenicity, baseline seizure frequency. Four of the seven discussed have been previously related to other neurologic diseases. Future investigation of these genes could establish new biomarkers for predicting epileptogenicity, and could have significant implications for diagnosis and management of temporal lobe epilepsy, as well as epilepsy pathogenesis.
authors.affiliation: College of Medicine, University of Arizona, Tucson, AZ, USA. Electronic address: apmccall@email.arizona.edu.
authors.forename: Abigail P
authors.initials: AP
authors.lastname: McCallum
authors.affiliation: College of Nursing, University of Arizona, PO Box 210203, Tucson, AZ 85721, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gallek
authors.affiliation: College of Medicine, Department of Surgery, Division of Neurosurgery, University of Arizona, PO Box 245070, Tucson, AZ 85724, USA.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Ramey
authors.affiliation: Informatics/Bioinformatics Shared Services, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA. Electronic address: uacc-bisr@uacc.arizona.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: Manziello
authors.affiliation: College of Medicine, Department of Surgery, University of Arizona, PO Box 245072, Tucson, AZ 85724, USA.
authors.forename: Marlys H
authors.initials: MH
authors.lastname: Witte
authors.affiliation: College of Medicine, Department of Surgery, University of Arizona, PO Box 245072, Tucson, AZ 85724, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bernas
authors.affiliation: College of Medicine, Department of Neurology, University of Arizona, PO Box 245023, Tucson, AZ 85724, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Labiner
authors.affiliation: College of Medicine, Department of Surgery, Division of Neurosurgery, University of Arizona, PO Box 245070, Tucson, AZ 85724, USA.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Weinand
keywords: Amygdalohippocampectomy; Epileptogenicity; Gene expression; Neurosurgical genomics; Temporal lobectomy