title: Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis.
abstract: Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca(2+)-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca(2+) 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.
authors.affiliation: Laboratory for Neurobiology, Experimental Neurology, University of Leuven, Leuven, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Bogaert
authors.forename: An
authors.initials: A
authors.lastname: Goris
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.forename: Veerle
authors.initials: V
authors.lastname: Geelen
authors.forename: Robin
authors.initials: R
authors.lastname: Lemmens
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Nathalie
authors.initials: N
authors.lastname: Verpoorten
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: John E
authors.initials: JE
authors.lastname: Landers
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Shaw
authors.forename: Anna
authors.initials: A
authors.lastname: Birve
authors.forename: Peter M
authors.initials: PM
authors.lastname: Andersen
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Slowik
authors.forename: Barbara
authors.initials: B
authors.lastname: Tomik
authors.forename: Judith
authors.initials: J
authors.lastname: Melki
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D001530:Belgium / Q000453:epidemiology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018091:Receptors, AMPA / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2
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