Identifying a gene expression signature of cluster headache in blood

Eising, Else; Pelzer, Nadine; Vijfhuizen, Lisanne S.; Vries, Boukje de; Ferrari, Michel D.; Hoen, Peter A.C. ‘t; Terwindt, Gisela M.; Maagdenberg, Arn M. J. M. van den

doi:10.1038/srep40218

Cited by 22 publications

(15 citation statements)

References 58 publications

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“…Molecular profiles of circulating blood were suggested to reflect pathological events throughout the organism. Growing evidence demonstrates the existence of gene expression signatures characteristic for certain disease phenotypes or environmental influences [10][11][12][13]. Moreover, researchers compared the peripheral blood transcriptome to gene expression patterns in nine different human tissues, demonstrating that more than 80% of expressed genes are shared between blood and any of the tissues [14].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Paczkowska-Abdulsalam

Niemira

Bielska

et al. 2020

IJMS

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Multiple mechanisms have been suggested to confer to the pathophysiology of metabolic syndrome (MetS), however despite great interest from the scientific community, the exact contribution of each of MetS risk factors still remains unclear. The present study aimed to investigate molecular signatures in peripheral blood of individuals affected by MetS and different degrees of obesity. Metabolic health of 1204 individuals from 1000PLUS cohort was assessed, and 32 subjects were recruited to four study groups: MetS lean, MetS obese, “healthy obese”, and healthy lean. Whole-blood transcriptome next generation sequencing with functional data analysis were carried out. MetS obese and MetS lean study participants showed the upregulation of genes involved in inflammation and coagulation processes: granulocyte adhesion and diapedesis (p < 0.0001, p = 0.0063), prothrombin activation pathway (p = 0.0032, p = 0.0091), coagulation system (p = 0.0010, p = 0.0155). The results for “healthy obese” indicate enrichment in molecules associated with protein synthesis (p < 0.0001), mitochondrial dysfunction (p < 0.0001), and oxidative phosphorylation (p < 0.0001). Our results suggest that MetS is related to the state of inflammation and vascular system changes independent of excess body weight. Furthermore, “healthy obese”, despite not fulfilling the criteria for MetS diagnosis, seems to display an intermediate state with a lower degree of metabolic abnormalities, before they proceed to a full blown MetS.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Paczkowska-Abdulsalam

Niemira

Bielska

et al. 2020

IJMS

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“…These findings suggest the involvement of the RAMP1 gene in the CH pathophysiology and further studies are wanted in order to confirm this hypothesis. There are so far only three published studies on broad screenings for genes differentially transcribed between individuals with CH and controls [112][113][114]. Neither of these three studies reports differences in gene expression of CGRP or any of its receptor components.…”

Section: Cgrp and Geneticsmentioning

confidence: 99%

Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache

2020

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Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.

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“…Also signaling pathways were present among the DE genes. One of the Notch signaling genes, MAML2, was also differentially expressed in cluster headache patients 32 . The Notch signaling pathway has previously been associated with migraine, among others due to the GWAS hit near NOTCH4 1 and a mutation in NOTCH3 results in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) with migraine as one of the main symptoms.…”

Section: Changes At Gene Level During the Migraine Attackmentioning

confidence: 98%

Changes in the gene expression profile during spontaneous migraine attacks

Kogelman

Falkenberg

Buil

et al. 2020

Preprint

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Objective. Migraine occurs in clearly defined attacks and thus lends itself to investigate changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore is likely to reveal changes during a migraine attack. We examined the hypothesis that changes in RNA expression during and outside of a spontaneous migraine attack exist which are specific to the migraine attack. Methods.We collected blood samples from 27 migraine patients during an attack, two hours after treatment with subcutaneous sumatriptan, on a headache-free day and after a cold pressor test. All patients were deeply phenotyped, including headache characteristics and treatment effect during the sampling. RNA-Sequencing, genotyping, and steroid profiling was performed on all samples. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and we integrated transcriptomic and genomic data.Results. We found 29 differentially expressed (DE) genes between 'attack' and 'after treatment', after subtracting non-migraine specific genes, i.e. genes related to a general pain/stress response. DE genes were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed molecular mechanisms affected by change in gene interactions during the migraine attack, e.g. 'ion transmembrane transport' and 'response to stress'. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. '5HT1 type receptor mediated signaling pathway'.Interpretation. Using a paired-sample design, we uniquely investigated intra-individual changes in the gene expression during a migraine attack. We revealed both genes and pathway potentially involved in the pathophysiology of migraine.

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Identifying a gene expression signature of cluster headache in blood

Cited by 22 publications

References 58 publications

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache

Changes in the gene expression profile during spontaneous migraine attacks

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