Temporal Lobe Epilepsy and Matrix Metalloproteinase 9: A tempting relation but negative genetic association

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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. Material and 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. Conclusion: 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. © 2010 British Epilepsy Association.

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Heuser, K., Hoddevik, E. H., Taubøll, E., Gjerstad, L., Indahl, U., Kaczmarek, L., … Ottersen, O. P. (2010). Temporal Lobe Epilepsy and Matrix Metalloproteinase 9: A tempting relation but negative genetic association. Seizure, 19(6), 335–338. https://doi.org/10.1016/j.seizure.2010.05.003

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