Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis.
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.
Bogaert
Elke
E
Laboratory for Neurobiology, Experimental Neurology, University of Leuven, Leuven, Belgium.
Goris
An
A
Van Damme
Philip
P
Geelen
Veerle
V
Lemmens
Robin
R
van Es
Michael A
MA
van den Berg
Leonard H
LH
Sleegers
Kristel
K
Verpoorten
Nathalie
N
Timmerman
Vincent
V
De Jonghe
Peter
P
Van Broeckhoven
Christine
C
Traynor
Bryan J
BJ
Landers
John E
JE
Brown
Robert H
RH
Glass
Jonathan D
JD
Al-Chalabi
Ammar
A
Shaw
Christopher E
CE
Birve
Anna
A
Andersen
Peter M
PM
Slowik
Agnieszka
A
Tomik
Barbara
B
Melki
Judith
J
Robberecht
Wim
W
Van Den Bosch
Ludo
L
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
D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2
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