Genetics of Cluster Headache

Schürks, Markus

doi:10.1007/s11916-010-0096-8

Cited by 23 publications

(6 citation statements)

References 47 publications

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“…The characteristic circadian and circannual periodicity of CH attacks and accompanying autonomic symptoms implicate the involvement of the hypothalamus in the disorder (1,8 9…”

Section: Pathophysiologymentioning

confidence: 99%

Genetics of cluster headache

et al. 2019

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Background Cluster headache is the most severe primary headache disorder. A genetic basis has long been suggested by family and twin studies; however, little is understood about the genetic variants that contribute to cluster headache susceptibility. Methods We conducted a literature search of the MEDLINE database using the PubMed search engine to identify all human genetic studies for cluster headache. In this article we provide a review of those genetic studies, along with an overview of the pathophysiology of cluster headache and a brief review of migraine genetics, which have both been significant drivers of cluster headache candidate gene selection. Results The investigation of cluster headache genetic etiology has been dominated by candidate gene studies. Candidate selection has largely been driven by the pathophysiology, such as the striking rhythmic nature of the attacks, which spurred close examination of the circadian rhythm genes CLOCK and HCRTR2. More recently, unbiased genetic approaches such as genome-wide association studies (GWAS) have yielded new genetic avenues of interest including ADCYAP1R1 and MME. Conclusions The majority of candidate genes studied for cluster headache suffer from poor reproducibility. Broader genetic interrogation through larger unbiased GWAS, exome, and whole genome studies may provide more robust candidates, and in turn provide a clearer understanding of the causes of cluster headache.

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“…The characteristic circadian and circannual periodicity of CH attacks and accompanying autonomic symptoms implicate the involvement of the hypothalamus in the disorder (1,8 9…”

Section: Pathophysiologymentioning

confidence: 99%

Genetics of cluster headache

et al. 2019

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“…The etiology and pathogenic mechanism of cluster headache has been not clarified absolutely, however, recent research has shown that genetic and environmental factors have potential relations with CH [ 3 ]. Currently, about 5%-20% of CH patients had CH family history.…”

Section: Introductionmentioning

confidence: 99%

Genetic association of HCRTR2, ADH4 and CLOCK genes with cluster headache: a Chinese population-based case-control study

et al. 2018

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BackgroundCluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility. A large numbers of genetic association studies have confirmed that the HCRTR2 (Hypocretin Receptor 2) SNP rs2653349, and the ADH4 (Alcohol Dehydrogenase 4) SNP rs1126671 and rs1800759 polymorphisms are linked to CH. In addition, the CLOCK (Circadian Locomotor Output Cycles Kaput) gene is becoming a research hotspot for CH due to encoding a transcription factor that serves as a basic driving force for circadian rhythm in humans. The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4 and CLOCK genes in a Chinese CH case–control sample.MethodsWe genotyped polymorphisms of nine single nucleotide polymorphisms (SNPs) in the HCRTR2, ADH4 and CLOCK genes to perform an association study on a Chinese Han CH case-control sample (112 patients and 192 controls),using Sequenom MALDI-TOF mass spectrometry iPLEX platform. The frequencies and distributions of genotypes and haplotypes were statistically compared between the case and control groups to identify associations with CH. The effects of SNPs on CH were further investigated by multiple logistic regression.ResultsThe frequency of the HCRTR2 SNP rs3800539 GA genotype was significantly higher in cases than in controls (48.2% vs.37.0%). The GA genotypes was associated with a higher CH risk (OR = 1.483, 95% CI: 0.564-3.387, p = 0.038), however, after Bonferroni correction, the association lost statistical significance. Haplotype analysis of the HCRTR2 SNPs showed that among eight haplotypes, only H1-GTGGGG was linked to a reduced CH risk (44.7% vs. 53.1%, OR = 0.689, 95% CI =0.491~0.966, p = 0.030). No significant association of ADH4, CLOCK SNPs with CH was statistically detected in the present study.ConclusionsAssociation between HCRTR2, ADH4,CLOCK gene polymorphisms and CH was not significant in the present study, however, haplotype analysis indicated H1-GTGGGG was linked to a reduced CH risk.Electronic supplementary materialThe online version of this article (10.1186/s10194-017-0831-1) contains supplementary material, which is available to authorized users.

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“…Activation of the trigeminovascular system and possibly associated inflammatory processes have been implicated in causing and aggravating the pain101112. Although family members of cluster headache patients seem to be at increased risk of developing cluster headache3, indicating contribution of genetic factors, genetic studies into cluster headache have been largely unsuccessful1314. Some studies suggested involvement of the HCRTR2 gene that encodes the hypocretin type 2 receptor, but this finding could not be confirmed in other studies15.…”

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confidence: 99%

Identifying a gene expression signature of cluster headache in blood

Eising

Pelzer

Vijfhuizen

et al. 2017

Sci Rep

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Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headache.

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Genetics of Cluster Headache

Cited by 23 publications

References 47 publications

Genetics of cluster headache

Genetics of cluster headache

Genetic association of HCRTR2, ADH4 and CLOCK genes with cluster headache: a Chinese population-based case-control study

Identifying a gene expression signature of cluster headache in blood

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