Evidence for an association between migraine and the hypocretin receptor 1 gene

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Abstract

The aim of our study was to investigate whether genetic variants in the hypocretin receptor 1 ( HCRTR1) gene could modify the occurrence and the clinical features of migraine. Using a case–control strategy we genotyped 384 migraine patients and 259 controls for three SNPs in the HCRTR1 gene. Genotypic and allelic frequencies of the rs2271933 non-synonymous polymorphism resulted different ( χ ² = 9.872, p = 0.007; χ ² = 8.108, p = 0.004) between migraineurs and controls. The carriage of the A allele was associated with an increased migraine risk (OR 1.42, 95% CI 1.11–1.81). When we divided the migraine patients into different subgroups, the difference reached the level of statistical significance only in migraine without aura. The different genotypes had no significant effect on the examined clinical characteristics of the disease. In conclusion, our data supports the hypothesis that the HCRTR1 gene could represent a genetic susceptibility factor for migraine without aura and suggests that the hypocretin system may have a role in the pathophysiology of migraine.

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Most cited references 37

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Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

T Sakurai, A Amemiya, M Ishii … (1998)

The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.

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The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

L de Lecea, T S Kilduff, C Peyron … (1998)

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.

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Lost productive time and cost due to common pain conditions in the US workforce.

Walter Stewart, Judith Ricci, Elsbeth Chee … (2003)

Common pain conditions appear to have an adverse effect on work, but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain. To measure lost productive time (absence and reduced performance due to common pain conditions) during a 2-week period. Cross-sectional study using survey data from the American Productivity Audit (a telephone survey that uses the Work and Health Interview) of working adults between August 1, 2001, and July 30, 2002. Random sample of 28 902 working adults in the United States. Lost productive time due to common pain conditions (arthritis, back, headache, and other musculoskeletal) expressed in hours per worker per week and calculated in US dollars. Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition. Headache was the most common (5.4%) pain condition resulting in lost productive time. It was followed by back pain (3.2%), arthritis pain (2.0%), and other musculoskeletal pain (2.0%). Workers who experienced lost productive time from a pain condition lost a mean (SE) of 4.6 (0.09) h/wk. Workers who had a headache had a mean (SE) loss in productive time of 3.5 (0.1) h/wk. Workers who reported arthritis or back pain had mean (SE) lost productive times of 5.2 (0.25) h/wk. Other common pain conditions resulted in a mean (SE) loss in productive time of 5.5 (0.22) h/wk. Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year. The majority (76.6%) of the lost productive time was explained by reduced performance while at work and not work absence. Pain is an inordinately common and disabling condition in the US workforce. Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance.

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Author and article information

Contributors

: +39-11-6638510 , +39-11-6963487 , irainero@molinette.piemonte.it

Journal

Journal ID (nlm-ta): J Headache Pain

Title: The Journal of Headache and Pain

Publisher: Springer Milan (Milan )

ISSN (Print): 1129-2369

ISSN (Electronic): 1129-2377

Publication date (Electronic): 23 February 2011

Publication date PMC-release: 23 February 2011

Publication date (Print): April 2011

Volume: 12

Issue: 2

Pages: 193-199

Affiliations

[1 ]Neurology II, Department of Neuroscience, University of Torino, Via Cherasco 15, 10126 Turin, Italy

[2 ]Mental Health Department, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy

Article

Publisher ID: 314

DOI: 10.1007/s10194-011-0314-8

PMC ID: 3072499

PubMed ID: 21344296

SO-VID: d9e92161-271e-4a18-9d27-72cb556db12b

History

Date received : 2 September 2010

Date accepted : 12 December 2010

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ScienceOpen disciplines: Anesthesiology & Pain management

Keywords: migraine with aura,genetic association studies,migraine without aura,hypocretin receptor 1,hypocretins

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ScienceOpen disciplines: Anesthesiology & Pain management

Keywords: migraine with aura, genetic association studies, migraine without aura, hypocretin receptor 1, hypocretins

Evidence for an association between migraine and the hypocretin receptor 1 gene

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Abstract

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Irish Journal of Paramedicine

Most cited references 37

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

Lost productive time and cost due to common pain conditions in the US workforce.

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