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Gamma-aminobutyric acid (GABA) receptors GABRA4, GABRE, and GABRQ gene polymorphisms and risk for migraine

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Several biochemical, pharmacological, neurophysiological and experimental data suggest a possible role of gamma-aminobutyric acid (GABA) in the pathogenesis of migraine. We investigated the possible association of the most common single nucleotide polymorphisms (SNPs) in the GABA receptor alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) genes with the risk for migraine. A TaqMan-based qPCR assay designed to detect the most common SNPs in the GABRA4 (rs2229940), GABRE (rs1139916), and GABRQ (rs3810651) was performed in 197 migraine patients and 394 age- and gender-matched controls. The possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes was also studied. The frequency of GABRE rs1139916AA genotype was significantly lower in the migraine group only in the female gender, but the differences did not reach statistical significance after correction for multiple comparisons. The mean ± SD age at onset of migraine was significantly lower in patients with GABRQ rs3810651AA as compared with the other two genotypes. Positive family history of migraine and presence or absence of aura did not influence the frequencies of the genotypes of the three SNPs studied. Triggering of migraine by ethanol was significantly less frequent in patients with GABRA4 rs2229940GG and more frequent in patients with GABRQ 3810651TT genotype, but the differences lost statistical significance after correction for multiple comparisons. GABRQ rs3810651 could play a role in the modification of age at onset of migraine.

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Acknowledgements

This work was supported by Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (Grants PI12/00241, PI12/00324, PI15/00303, RETICS RD12/0013/0002, and RETICS RD16/0006/0004) and Junta de Extremadura, Mérida, Spain (Grants GR15026 and IB16170). Financed in part with FEDER funds from the European Union.

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Authors and Affiliations

  1. Department of Pharmacology, University of Extremadura, Cáceres, Spain

    Elena García-Martín, Gara Esguevillas, Gemma Amo & José A. G. Agúndez

  2. Red de Investigación de reacciones adversas a alergenos y fármacos, Instituto de Salud Carlos III, Madrid, Spain

    Elena García-Martín & José A. G. Agúndez

  3. AMGenomics, Edificio Tajo, Avda. de la Universidad s/n, Cáceres, Spain

    Elena García-Martín & José A. G. Agúndez

  4. Department of Family Medicine, Hospital “Príncipe de Asturias”, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain

    Mercedes Serrador

  5. Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, C/Marroquina 14, 3° B, 28030, Madrid, Spain

    Hortensia Alonso-Navarro, Francisco Navacerrada & Félix Javier Jiménez-Jiménez

  6. Department of Medicine-Neurology, Hospital “Príncipe de Asturias”, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain

    Hortensia Alonso-Navarro, Esteban García-Albea & Félix Javier Jiménez-Jiménez

  7. Service of Neurology, Hospital “Ramón y Cajal”, Universidad de Alcalá, Madrid, Spain

    Francisco Navacerrada

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  1. Elena García-Martín
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  2. Gara Esguevillas
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  3. Mercedes Serrador
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  4. Hortensia Alonso-Navarro
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  5. Francisco Navacerrada
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  7. Esteban García-Albea
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  8. José A. G. Agúndez
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  9. Félix Javier Jiménez-Jiménez
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Correspondence to Félix Javier Jiménez-Jiménez.

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García-Martín, E., Esguevillas, G., Serrador, M. et al. Gamma-aminobutyric acid (GABA) receptors GABRA4, GABRE, and GABRQ gene polymorphisms and risk for migraine. J Neural Transm 125, 689–698 (2018). https://doi.org/10.1007/s00702-017-1834-4

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  • DOI: https://doi.org/10.1007/s00702-017-1834-4

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