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Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis |
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| Authors: | Elke Bogaert An Goris Philip Van Damme Veerle Geelen Robin Lemmens Michael A. van EsLeonard H. van den Berg Kristel Sleegers Nathalie Verpoorten Vincent Timmerman Peter De Jonghe Christine Van Broeckhoven Bryan J. TraynorJohn E. Landers Robert H. Brown Jr.Jonathan D. Glass Ammar Al-ChalabiChristopher E. Shaw Anna BirvePeter M. Andersen Agnieszka SlowikBarbara Tomik Judith MelkiWim Robberecht Ludo Van Den Bosch |
| Affiliation: | a Laboratory for Neurobiology, Experimental Neurology, University of Leuven, Leuven, Belgium b Vesalius Research Center, VIB, Leuven, Belgium c Laboratory for Neuroimmunology, Section for Experimental Neurology, University of Leuven, Leuven, Belgium d Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands e Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium f Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium g Peripheral Neuropathy Group, Department of Molecular Genetics, VIB, Antwerp, Belgium h Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium i Division of Neurology, University Hospital of Antwerp, Antwerp, Belgium j Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, NIA, Bethesda, Maryland, United States k Cecil B. Day Laboratory for Neuromuscular Research, University of Massachusetts Medical School, Worcester, Massachusetts, United States l Department of Neurology, Emory University, Atlanta, Georgia, United States m MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, Department of Clinical Neuroscience, London, United Kingdom n Institute of Clinical Neuroscience, Umeå University, Umeå, Sweden o Department of Neurology, Jagiellonian University, Krakow, Poland p INSERM U-788 and University of Paris 11, Le Kremlin-Bicêtre, France q Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium |
| Abstract: | Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca2+ permeability is determined by the GluR2 subunit. We investigated whether polymorphisms or mutations in the GluR2 gene (GRIA2) predispose patients to ALS. Upon sequencing 24 patients and 24 controls no nonsynonymous coding variants were observed but 24 polymorphisms were identified, 9 of which were novel. In a screening set of 310 Belgian ALS cases and 794 healthy controls and a replication set of 3157 cases and 5397 controls from 6 additional populations no association with susceptibility, age at onset, or disease duration was observed. We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS. |
| Keywords: | Amyotrophic lateral sclerosis Excitotoxicity GluR2 Motor neuron |
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