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The Journal of Headache and Pain logoLink to The Journal of Headache and Pain
. 2007 Jun 11;8(3):152–156. doi: 10.1007/s10194-007-0383-x

Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis

Innocenzo Rainero 1,, Elisa Rubino 1, Walter Valfrè 1, Salvatore Gallone 1, Paola De Martino 1, Erika Zampella 1, Lorenzo Pinessi 1
PMCID: PMC3476142  PMID: 17563843

Abstract

The objective of this study was to investigate the association between polymorphisms of the hypocretin receptor 2 gene (HCRTR2) and the risk of cluster headache (CH). The study is a meta-analysis of published case-control studies investigating the association between polymorphisms of the HCRTR2 gene and CH. Pooled odds ratios (OR) were estimated using both random (RE) and fixed effects (FE) models. Three studies, performed in five different European countries, with 593 cases and 599 controls, were included in the study. Allele G of the G1246A HCRTR2 polymorphism was significantly associated with CH (FE OR 1.58, CI 95% 1.27–1.95; RE OR 1.55 (1.14–2.12)). Carriers of the GG genotype showed a higher disease risk compared to the remaining genotypes (FE OR 1.75, CI 95% 1.37–2.25; RE OR 1.69, CI 95% 1.11–2.58). Our data confirm that the G1246A polymorphism of the HCRTR2 gene may modulate the genetic risk for CH.

Keywords: Meta-analysis, Genetic association, Cluster headache, G1246A polymorphism, Hypocretin receptor 2 gene

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References

  • 1.Goadsby P.J. Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol. 2002;1:251–257. doi: 10.1016/S1474-4422(02)00104-7. [DOI] [PubMed] [Google Scholar]
  • 2.Torelli P., Beghi E., Manzoni G.C. Cluster headache prevalence in the Italian general population. Neurology. 2005;64:469–474. doi: 10.1212/01.WNL.0000150901.47293.BC. [DOI] [PubMed] [Google Scholar]
  • 3.Russell M.B., Andersson P.G., Thomsen L.L. Familial occurrence of cluster headache. J Neurol Neurosurg Psychiatry. 1995;58:341–343. doi: 10.1136/jnnp.58.3.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Leone M., Russell M.B., Rigamonti A., et al. Increased familial risk of cluster headache. Neurology. 2001;56:1233–1236. doi: 10.1212/wnl.56.9.1233. [DOI] [PubMed] [Google Scholar]
  • 5.Amrani M., Ducros A., Boulan P., et al. Familial cluster headache: a series of 186 index patients. Headache. 2002;42:974–977. doi: 10.1046/j.1526-4610.2002.02226.x. [DOI] [PubMed] [Google Scholar]
  • 6.Russell M.B., Andersson P.G., Thomsen L.L., Iselius L. Cluster headache is an autosomal dominantly inherited disorder in some families: a complex segregation analysis. J Clin Genet. 1995;32:954–956. doi: 10.1136/jmg.32.12.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Pinessi L., Rainero I., Rivoiro C., et al. Genetics of cluster headache: an update. J Headache Pain. 2005;6:234–236. doi: 10.1007/s10194-005-0194-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Russell M.B. Epidemiology and genetics of cluster headache. Lancet Neurol. 2004;3:279–283. doi: 10.1016/S1474-4422(04)00735-5. [DOI] [PubMed] [Google Scholar]
  • 9.Sakurai T., Amemiya A., Ishii M., et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573–585. doi: 10.1016/S0092-8674(00)80949-6. [DOI] [PubMed] [Google Scholar]
  • 10.Nishino S. The hypocretin/orexin system in health and disease. Biol Psychiatry. 2003;54:87–95. doi: 10.1016/S0006-3223(03)00349-4. [DOI] [PubMed] [Google Scholar]
  • 11.Martynska L., Wolinska-Witort E., Chmielowska M., et al. The physiological role of orexins. Neuro Endocrinol Lett. 2005;26:289–292. [PubMed] [Google Scholar]
  • 12.Bingham S., Davey P.T., Babbs A.J., et al. Orexin-A, an hypothalamic peptide with analgesic properties. Pain. 2001;92:81–90. doi: 10.1016/S0304-3959(00)00470-X. [DOI] [PubMed] [Google Scholar]
  • 13.Mobarakeh J.I., Takahashi K., Sakurada S., et al. Enhanced antinociception by intracerebroventricularly and intrathecally administered orexin A and B (hypocretin-1 and-2) in mice. Peptides. 2005;26:767–777. doi: 10.1016/j.peptides.2005.01.001. [DOI] [PubMed] [Google Scholar]
  • 14.Rainero I., Gallone S., Valfrè W., et al. A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache. Neurology. 2004;63:1286–1288. doi: 10.1212/01.wnl.0000142424.65251.db. [DOI] [PubMed] [Google Scholar]
  • 15.Schurks M., Kurth T., Geissler I., et al. Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene. Neurology. 2006;66:1917–1919. doi: 10.1212/01.wnl.0000215852.35329.34. [DOI] [PubMed] [Google Scholar]
  • 16.Baumber L., Sjostrand C., Leone M., et al. A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort. Neurology. 2006;66:1888–1893. doi: 10.1212/01.wnl.0000219765.95038.d7. [DOI] [PubMed] [Google Scholar]
  • 17.Munafo M.R., Flint J. Meta-analysis of genetic association studies. Trends Genet. 2004;20:439–444. doi: 10.1016/j.tig.2004.06.014. [DOI] [PubMed] [Google Scholar]
  • 18.Headache Classification Subcommittee of the International Headache Society The International Classification of Headache Disorders. Cephalalgia. 2004;24([Suppl1]):9–160. doi: 10.1111/j.1468-2982.2003.00824.x. [DOI] [PubMed] [Google Scholar]
  • 19.Siegel J.M. Hypocretin (orexin): role in normal behavior and neuropathology. Annu Rev Psychol. 2004;55:125–148. doi: 10.1146/annurev.psych.55.090902.141545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Smart D., Jerman J. The physiology and pharmacology of the orexins. Pharmacol Ther. 2002;94:51–61. doi: 10.1016/S0163-7258(02)00171-7. [DOI] [PubMed] [Google Scholar]
  • 21.Kohlmeier K.A., Inoue T., Leonard C.S. Hypocretin/orexin peptide signaling in the ascending arousal system: elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum. J Neurophysiol. 2004;92:221–235. doi: 10.1152/jn.00076.2004. [DOI] [PubMed] [Google Scholar]
  • 22.Peyron C., Tighe D.K., Pol A.N., et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18:9996–10015. doi: 10.1523/JNEUROSCI.18-23-09996.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Fadel J., Pasumarthi R., Reznikov L.R. Stimulation of cortical acetylcholine release by orexin A. Neuroscience. 2005;130:541–547. doi: 10.1016/j.neuroscience.2004.09.050. [DOI] [PubMed] [Google Scholar]
  • 24.Lecea L., Kilduff T.S., Peyron C., et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA. 1998;95:322–327. doi: 10.1073/pnas.95.1.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Nasman J., Bart G., Larsson K., et al. The orexin OX1 receptor regulates Ca2+ entry via diacylglycerol-activated channels in differentiated neuroblastoma cells. J Neurosci. 2006;26:10658–10666. doi: 10.1523/JNEUROSCI.2609-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]

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