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The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups

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Abstract

Migraine is a painful and debilitating disorder with a significant genetic component. Steroid hormones, in particular estrogen, have long been considered to play a role in migraine, as variations in hormone levels are associated with migraine onset in many sufferers of the disorder. Steroid hormones mediate their activity via hormone receptors, which have a wide tissue distribution. Estrogen receptors have been localized to the brain in regions considered to be involved in migraine pathogenesis. Hence it is possible that genetic variation in the estrogen receptor gene may play a role in migraine susceptibility. This study thus examined the estrogen receptor 1 (ESRα) gene for a potential role in migraine pathogenesis and susceptibility. A population-based cohort of 224 migraine sufferers and 224 matched controls were genotyped for the G594A polymorphism located in exon 8 of the ESR1 gene. Statistical analysis indicated a significant difference between migraineurs and non-migraineurs in both the allele frequencies (P=0.003) and genotype distributions (P=0.008) in this sample. An independent follow-up study was then undertaken using this marker in an additional population-based cohort of 260 migraine sufferers and 260 matched controls. This resulted in a significant association between the two groups with regard to allele frequencies (P=8×10−6) and genotype distributions (P=4×10−5). Our findings support the hypothesis that genetic variation in hormone receptors, in particular the ESR1 gene, may play a role in migraine.

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Acknowledgements

This work was supported by funding from NHMRC and Griffith University. Dr. Rod Lea is supported by an NHMRC (C.J. Martin) Fellowship. Experiments comply with the current laws in Australia.

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Authors and Affiliations

  1. Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia

    Natalie J. Colson, Rod A. Lea, Sharon Quinlan & Lyn R. Griffiths

  2. Institute of Molecular Systematics, School of Biological Sciences, Victoria University of Wellington, New Zealand

    Rod A. Lea

  3. Queensland Clinical Genetics Service, Royal Children’s Hospital, Queensland, Australia

    John MacMillan

Authors
  1. Natalie J. Colson
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  2. Rod A. Lea
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  3. Sharon Quinlan
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  4. John MacMillan
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  5. Lyn R. Griffiths
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Correspondence to Lyn R. Griffiths.

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Colson, N.J., Lea, R.A., Quinlan, S. et al. The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups. Neurogenetics 5, 129–133 (2004). https://doi.org/10.1007/s10048-004-0181-4

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  • DOI: https://doi.org/10.1007/s10048-004-0181-4

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