Genetics of Cluster Headache
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Cluster headache (CH) is a rare, excruciating primary headache disorder. A genetic basis has been suggested by family and twin studies, but the mode of transmission seems to vary and the amount of heritability is unclear. The number of genetic association studies investigating variants implicated in the pathophysiology of CH is limited. The HCRTR2 1246G > A and the ADH4 925A > G polymorphisms have been associated with CH. The former has been confirmed and may affect the hypothalamic hypocretin system. However, it only appears to account for a part of the genetic susceptibility for CH, and additional genetic and environmental factors are likely implicated. Pharmacogenetic studies have suggested that the GNB3 825C > T polymorphism may modify treatment response to triptans among CH patients by altering the signal transduction cascade via G protein–coupled receptors. Genetic studies in CH are notoriously difficult due to the complex nature of the disorder and the low prevalence of CH.
KeywordsCluster headache Gene variants G proteins Hypocretin Heritability Association studies
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- 3.Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders, 2nd edn. Cephalalgia 2004, 24(Suppl 1):9–160.Google Scholar
- 7.Ekbom K, Greitz T: Carotid angiography in cluster headache. Acta Radiol Diagn (Stockh) 1970, 10:177–186.Google Scholar
- 8.Goadsby PJ, Edvinsson L: Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain 1994, 117:427–434.Google Scholar
- 14.Nishino S: The hypocretin/orexin system in health and disease. Biol Psychiatry 2003, 54:87–95. (Published erratum in Biol Psychiatry 2003, 54:175.)Google Scholar
- 16.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, 92:1 page following 696.Google Scholar
- 25.Rainero I, Rubino E, Gallone S, et al.: Cluster headache is associated with the alcohol dehydrogenase 4 (ADH4) gene. Headache 2009, Nov 17 (Epub ahead of print).Google Scholar
- 26.Summ O, Gregor N, Marziniak M, et al.: Cluster headache and alpha 1-antitrypsin deficiency. Cephalalgia 2009 Jun 8 (Epub ahead of print).Google Scholar
- 32.• Rainero I, Rubino E, Valfre W, et al.: Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis. J Headache Pain 2007, 8:152–156. This meta-analysis underlines the role of the HCRTR2 1246G > A polymorphism in CH. CrossRefPubMedGoogle Scholar