Variations in the cannabinoid receptor 1 gene predispose to migraine

Juhász, Gabriella; Lazáry, Judit; Chase, Diana; Pegg, Emily; Downey, Darragh; Tóth, Zoltán; Stones, Kathryn; Platt, Hazel; Mekli, Krisztina; Payton, Antony; Anderson, Ian M.; Deakin, Bill; Bagdy, György

doi:10.1016/j.neulet.2009.06.021

Cited by 53 publications

(45 citation statements)

References 32 publications

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“…In our previous smaller study, we found direct effects of CNR1 gene on migraine only when using extreme trait combinations (0 symptoms vs. 3 symptoms on ID‐Migraine questionnaire) and haplotype analysis of the CNR1 gene. Even in this case, in the extended sample (including those who has only 1 or 2 symptoms) the distribution of association patterns with other migraine related symptoms were uneven (Juhasz et al 2009b) suggesting that this gene has a selective pathophysiological role.…”

Section: Discussionmentioning

confidence: 85%

“…All statistical testing adopted two‐tailed P = 0.05 threshold. For display purposes, in all three RLE severity categories, we calculated positive likelihood ratios (LR+) for significant genotypes and haplotypes by dividing the genotype/haplotype frequencies in possible migraine cases/symptom carriers by those in control subjects/non‐carriers, as previously described (Juhasz et al 2009b). …”

Section: Methodsmentioning

confidence: 99%

“…In addition, CNR1 genetic variants in interaction with recent negative life events (RLE) increased the risk of depression (Juhasz et al 2009a), and in interaction with the serotonin transporter functional polymorphism ( 5HTTLPR) exerted anxiogenic effects (Lazary et al 2009, 2011). Regarding migraine, we demonstrated that a CNR1 haplotype increased the risk of migraine headaches (Juhasz et al 2009b). However, recent migraine GWAS studies could not identify risk genetic variants within the endocannabinoid system (Anttila et al 2013; Gormley et al 2016).…”

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confidence: 99%

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Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

Juhász

Csépány

Magyar

et al. 2016

Genes Brain and Behavior

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One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross‐sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID‐Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression‐ and anxiety‐related phenotypes. In addition, a Bayesian systems‐based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

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Section: Discussionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

Juhász

Csépány

Magyar

et al. 2016

Genes Brain and Behavior

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“…This receptor has an intriguing role in analgesia, and CNR1 variations have been previously demonstrated in various chronic pain conditions including migraine [56], irritable bowel syndrome (IBS) [57], and post-traumatic stress disorder (PTSD) [58]. FMS has been hypothesized to be the result of a clinical endocannabinoid-deficient state [58]; however, increased circulating levels of anandamide, a major endocannabinoid, have been found among FMS patients [59], possibly representing an autoregulatory response to pain.…”

Section: Role Of the Catechol-o-methyltransferase Gene Polymorphism Imentioning

confidence: 99%

Update on the genetics of the fibromyalgia syndrome

Ablin

Buskila

2015

Best Practice & Research Clinical Rheumatology

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“…Previous investigations have evaluated, among others, the association between the 1359 G/A polymorphism in syndromes implicated in mental disorders and related diseases such as schizophrenia, drug abuse, severe alcohol withdrawal, migraine, osteoporosis and Gilles de la Tourette syndrome [23][24][25][26][27][28]. However, a direct role of this SNP of the CNR1 gene in disease has still to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%