title: Association of a GRIA3 gene polymorphism with migraine in an Australian case-control cohort.
abstract: BACKGROUND
  The excitatory neurotransmitter glutamate has been implicated in both the hyperexcitability required for cortical spreading depression as well as activation of the trigeminovascular system required for the allodynia associated with migraine. Polymorphisms in the glutamate receptor ionotropic amino-3-hydroxy-5-methyl-4-isoxazole-propionin acid 1 (GRIA1) and GRIA3 genes that code for 2 of 4 subunits of the glutamate receptor have been previously associated with migraine in an Italian population. In addition, the GRIA3 gene is coded within a previously identified migraine susceptibility locus at Xq24. This study investigated the previously associated polymorphisms in both genes in an Australian case-control population.
  
  
  METHODS
  Variants in GRIA1 and GRIA3 were genotyped in 472 unrelated migraine cases and matched controls, and data were analyzed for association.
  
  
  RESULTS
  Analysis showed no association between migraine and the GRIA1 gene. However, association was observed with the GRIA3 single nucleotide polymorphism (SNP) rs3761555 (P=.008).
  
  
  CONCLUSIONS
  The results of this study confirmed the previous report of association at the rs3761555 SNP within the migraine with aura subgroup of migraineurs. However, the study identified association with the inverse allele suggesting that rs3761555 may not be the causative SNP but is more likely in linkage disequilibrium with another causal variant in both populations. This study supports the plethora of evidence suggesting that glutamate dysfunction may contribute to migraine susceptibility, warranting further investigation of the glutamatergic system and particularly of the GRIA3 gene.
authors.affiliation: Genomics Research Centre, Griffith Health Institute, Griffith University, Southport, QLD, Australia.
authors.forename: Bridget H
authors.initials: BH
authors.lastname: Maher
authors.forename: Rod A
authors.initials: RA
authors.lastname: Lea
authors.forename: Jordan
authors.initials: J
authors.lastname: Follett
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Cox
authors.forename: Francesca
authors.initials: F
authors.lastname: Fernandez
authors.forename: Teresa
authors.initials: T
authors.lastname: Esposito
authors.forename: Fernando
authors.initials: F
authors.lastname: Gianfrancesco
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D001315:Australia / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018091:Receptors, AMPA / Q000235:genetics*
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3
keywords: GRIA1; GRIA3; glutamate; migraine