Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility

Daniela Formicola, Andrea Aloia, Simone Sampaolo, Olimpia Farina, Daria Diodato, Lyn R. Griffiths, Fernando Gianfrancesco, Giuseppe Di Iorio, Teresa Esposito

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (AMPA, NMDA and kainate receptors) or G-protein coupled metabotropic receptors. Glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated.Methods: The association of polymorphic variants of GRIA1-GRIA4 genes which encode for the four subunits (GluR1-GluR4) of the alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor for glutamate was tested in migraineurs with and without aura (MA and MO) and healthy controls.Results: Two variants in the regulative regions of GRIA1 (rs2195450) and GRIA3 (rs3761555) genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively), but not associated with MO, suggesting their role in cortical spreading depression. Whereas the rs548294 variant in GRIA1 gene showed association primarily with MO phenotype, supporting the hypothesis that MA and MO phenotypes could be genetically related. These variants modify binding sites for transcription factors altering the expression of GRIA1 and GRIA3 genes in different conditions.Conclusions: This study represents the first genetic evidence of a link between glutamate receptors and migraine.

Original languageEnglish
Article number103
JournalBMC Medical Genetics
Volume11
Issue number1
DOIs
Publication statusPublished - Jun 25 2010

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Migraine Disorders
Glutamic Acid
AMPA Receptors
Genes
Glutamate Receptors
Cortical Spreading Depression
Isoxazoles
Phenotype
Kainic Acid Receptors
G-Protein-Coupled Receptors
N-Methyl-D-Aspartate Receptors
Neurotransmitter Agents
Epilepsy
Transcription Factors
Central Nervous System
Binding Sites

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility. / Formicola, Daniela; Aloia, Andrea; Sampaolo, Simone; Farina, Olimpia; Diodato, Daria; Griffiths, Lyn R.; Gianfrancesco, Fernando; Di Iorio, Giuseppe; Esposito, Teresa.

In: BMC Medical Genetics, Vol. 11, No. 1, 103, 25.06.2010.

Research output: Contribution to journalArticle

Formicola, D, Aloia, A, Sampaolo, S, Farina, O, Diodato, D, Griffiths, LR, Gianfrancesco, F, Di Iorio, G & Esposito, T 2010, 'Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility', BMC Medical Genetics, vol. 11, no. 1, 103. https://doi.org/10.1186/1471-2350-11-103
Formicola, Daniela ; Aloia, Andrea ; Sampaolo, Simone ; Farina, Olimpia ; Diodato, Daria ; Griffiths, Lyn R. ; Gianfrancesco, Fernando ; Di Iorio, Giuseppe ; Esposito, Teresa. / Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility. In: BMC Medical Genetics. 2010 ; Vol. 11, No. 1.
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