title: Temporal lobe epilepsy and matrix metalloproteinase 9: a tempting relation but negative genetic association.
abstract: OBJECTIVE
  Neuroplasticity can be defined as the ability of the brain to adapt to environmental impacts. These adaptations include synapse formation and elimination, cortical reorganization, and neurogenesis. In epilepsy these mechanisms may become detrimental and contribute to disease progression. It has been proposed that Matrix Metalloproteinase 9 (MMP-9), a proteinase that cleaves extracellular matrix molecules, may be critically involved in aberrant synaptic formation in hippocampi of patients with Temporal Lobe Epilepsy (TLE). Here we present a case-control study designed to identify possible variants of the MMP-9 gene associated with human TLE.
  
  
  METHODS
  218 Norwegian patients with TLE and 181 ethnically matched controls were compared in our association analysis. We also studied associations within two subgroups of TLE--Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS), and Temporal Lobe Epilepsy with childhood Febrile Seizures (TLE-FS). Single nucleotide polymorphisms (SNPs) were selected from HapMap and dbSNP databases for the MMP-9 gene on chromosome 20. We used standard haplotype analysis and multivariate explorative analysis.
  
  
  RESULTS
  There were no statistically significant associations between the analyzed SNPs in the MMP-9 gene and TLE, nor were any significant associations found with the two examined subgroups MTLE-HS and TLE-FS, confirmed by both analyses.
  
  
  CONCLUSIONS
  We could not identify any polymorphisms of the human MMP-9 gene that were associated with TLE, MTLE-HS or TLE-FS, in the selected SNPs. However, factors that influence MMP-9 gene expression, post-transcriptional modifications, or the balance between activation and inhibition of MMP-9 may play a role in the pathogenesis of TLE and other epileptic syndromes.
authors.affiliation: Department of Neurology, Division for Clinical Neuroscience, Oslo University Hospital, Rikshospitalet, and University of Oslo, Norway. kjell.heuser@oslo-universitetssykehus.no
authors.forename: Kjell
authors.initials: K
authors.lastname: Heuser
authors.forename: Eystein Hellstrøm
authors.initials: EH
authors.lastname: Hoddevik
authors.forename: Erik
authors.initials: E
authors.lastname: Taubøll
authors.forename: Leif
authors.initials: L
authors.lastname: Gjerstad
authors.forename: Ulf
authors.initials: U
authors.lastname: Indahl
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Paul R
authors.initials: PR
authors.lastname: Berg
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Lien
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Ottersen
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D003294:Seizures, Febrile / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D020780:Matrix Metalloproteinase 9