Association of aGRIA3Gene Polymorphism With Migraine in an Australian Case-Control Cohort

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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) andGRIA3genes that code for 2 of 4 subunits of the glutamate receptor have been previously associated with migraine in an Italian population. In addition, theGRIA3gene 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.


Variants inGRIA1andGRIA3were genotyped in 472 unrelated migraine cases and matched controls, and data were analyzed for association.


Analysis showed no association between migraine and theGRIA1gene. However, association was observed with theGRIA3single nucleotide polymorphism (SNP) rs3761555 (P= .008).


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 theGRIA3gene.

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