Variations in the cannabinoid receptor 1 gene predispose to migraine

G. Juhász, J. Lazáry, Diana Chase, Emma Pegg, Darragh Downey, Zoltan G. Toth, Kathryn Stones, Hazel Platt, Krisztina Mekli, Antony Payton, Ian M. Anderson, J. F William Deakin, G. Bagdy

Research output: Contribution to journalArticle

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Abstract

In animal models endogenous cannabinoids have an inhibitory effect on trigeminovascular activation through the cannabinoid receptor 1 (CB1), although there is no evidence of the potential role of CB1 in human migraine. In this study we applied single marker association and haplotypic trend regression analysis to investigate the relationship between the CB1 gene (CNR1) and headache with migraine symptoms (nausea, photophobia and disability, measured by the ID-migraine questionnaire). We identified our controls (CO = 684) as those who have not reported ID-migraine symptoms at all and defined migraine headache sufferers (M = 195) as those who reported all three symptoms. The CNR1 was covered by 10 SNPs located throughout the gene based on haplotype tagging (htSNP) and previous literature. Our results demonstrated a significant haplotypic effect of CNR1 on migraine headaches (p = 0.008, after permutation p = 0.017). This effect was independent of reported depression or drug/alcohol abuse although using neuroticism in the analysis as covariant slightly decreased this association (p = 0.027, permutated p = 0.052). These results suggest a significant effect of CNR1 on migraine headaches that might be related to the alteration of peripheral trigeminovascular activation. In addition, this is the first study to demonstrate the effectiveness of using trait components combinations to define extreme phenotypes with haplotype analysis in genetic association studies for migraine. However, further studies are needed to elucidate the role of CNR1 and the cannabinoid system in migraine.

Original languageEnglish
Pages (from-to)116-120
Number of pages5
JournalNeuroscience Letters
Volume461
Issue number2
DOIs
Publication statusPublished - Sep 11 2009

Fingerprint

Cannabinoid Receptors
Migraine Disorders
Genes
Cannabinoids
Haplotypes
Photophobia
Genetic Association Studies
Carbon Monoxide
Nausea
Alcoholism
Substance-Related Disorders
Single Nucleotide Polymorphism
Animal Models
Regression Analysis
Depression
Phenotype

Keywords

  • Cannabinoid receptor 1
  • Haplotype
  • Migraine
  • Neuroticism
  • Psychiatric co-morbidity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Variations in the cannabinoid receptor 1 gene predispose to migraine. / Juhász, G.; Lazáry, J.; Chase, Diana; Pegg, Emma; Downey, Darragh; Toth, Zoltan G.; Stones, Kathryn; Platt, Hazel; Mekli, Krisztina; Payton, Antony; Anderson, Ian M.; Deakin, J. F William; Bagdy, G.

In: Neuroscience Letters, Vol. 461, No. 2, 11.09.2009, p. 116-120.

Research output: Contribution to journalArticle

Juhász, G, Lazáry, J, Chase, D, Pegg, E, Downey, D, Toth, ZG, Stones, K, Platt, H, Mekli, K, Payton, A, Anderson, IM, Deakin, JFW & Bagdy, G 2009, 'Variations in the cannabinoid receptor 1 gene predispose to migraine', Neuroscience Letters, vol. 461, no. 2, pp. 116-120. https://doi.org/10.1016/j.neulet.2009.06.021
Juhász, G. ; Lazáry, J. ; Chase, Diana ; Pegg, Emma ; Downey, Darragh ; Toth, Zoltan G. ; Stones, Kathryn ; Platt, Hazel ; Mekli, Krisztina ; Payton, Antony ; Anderson, Ian M. ; Deakin, J. F William ; Bagdy, G. / Variations in the cannabinoid receptor 1 gene predispose to migraine. In: Neuroscience Letters. 2009 ; Vol. 461, No. 2. pp. 116-120.
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