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Association of a GRIA3 Gene Polymorphism With Migraine in an A ustralian Case‐Control Cohort
Author(s) -
Maher Bridget H.,
Lea Rod A.,
Follett Jordan,
Cox Hannah C.,
Fernandez Francesca,
Esposito Teresa,
Gianfrancesco Fernando,
Haupt Larisa M.,
Griffiths Lyn R.
Publication year - 2013
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/head.12151
Subject(s) - migraine with aura , cortical spreading depression , migraine , glutamate receptor , single nucleotide polymorphism , linkage disequilibrium , genetic association , genetics , population , glutamatergic , medicine , biology , genotype , gene , aura , receptor , environmental health
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 I talian population. In addition, the GRIA3 gene is coded within a previously identified migraine susceptibility locus at X q24. This study investigated the previously associated polymorphisms in both genes in an A ustralian 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). Conclusion 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.