Analysis of the DNA methylation pattern of the promoter region of calcitonin gene-related peptide 1 gene in patients with episodic migraine: An exploratory case-control study

Rubino, Elisa; Boschi, Silvia; Giorgio, Elisa; Pozzi, Elisa; Marcinnó, Andrea; Gallo, Eugenia; Roveta, Fausto; Grassini, Alberto; Brusco, Alfredo; Rainero, Innocenzo

doi:10.1016/j.ynpai.2022.100089

Cited by 12 publications

(7 citation statements)

References 32 publications

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“… 28 Research showed a different methylation pattern in two CpG sites at the proximal promoter region of the calcitonin related polypeptide alpha ( CALCA ) gene, which encodes calcitonin gene-related peptide (CGRP) in patients with episodic migraine. 29 In addition, DNA methylation levels at different CpG sites in the CALCA gene promoter was correlated with several clinical characteristics of migraine. 29 In agreement with this study, 29 a low methylation level was observed at the promoter region of the receptor activity modifying protein 1 gene, which encodes a key receptor subunit of CGRP in patients with migraine compared with controls.…”

Section: Discussionmentioning

confidence: 99%

“… 29 In addition, DNA methylation levels at different CpG sites in the CALCA gene promoter was correlated with several clinical characteristics of migraine. 29 In agreement with this study, 29 a low methylation level was observed at the promoter region of the receptor activity modifying protein 1 gene, which encodes a key receptor subunit of CGRP in patients with migraine compared with controls. 30 …”

Section: Discussionmentioning

confidence: 99%

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DNA methylation status of interspersed repetitive sequences in patients with migraine

et al. 2023

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Objective To analyse the methylation status of the Long Interspersed Nuclear Element-1 (LINE-1) and Short Interspersed Nuclear Element Alu (Alu) of peripheral blood mononuclear cells (PBMCs) from patients with migraine compared with healthy control subjects. Methods This case–control study recruited patients with migraine without aura and age-matched healthy control subjects. PBMCs were purified from peripheral blood samples. Methylation levels and patterns of LINE-1 and Alu sequences were evaluated using combined bisulfite restriction analysis-interspersed repetitive sequences polymerase chain reaction. Results A total of 84 patients with migraine and 82 age-matched healthy controls were enrolled in the study. High levels of unmethylated cytosines in both the LINE-1 and Alu repetitive elements were observed in the migraine group compared with the control subjects. In addition, a significant difference was detected in the methylation level of LINE-1 between TT and CC genotype groups of the methylenetetrahydrofolate reductase gene. Conclusions These results suggest that analysis of epigenetic biomarkers in PBMCs may help to identify patients at a higher risk of migraine development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DNA methylation status of interspersed repetitive sequences in patients with migraine

et al. 2023

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“…Finally, in the last study of DNA methylation in migraine, Rubino et al. (39) evaluated the DNA methylation status of the promoter region of CALCA, the gene encoding CGRP, by using bisulfide sequencing, in 22 episodic migraine patients and 20 healthy controls. Authors found lower methylation levels in 2 CpG sites at the proximal promoter region in patients, localized within the binding site of the transcription factor CREB, suggesting an increased transcription of the gene.…”

Section: Dna Methylation In Migrainementioning

confidence: 99%

The impact of epigenetic mechanisms in migraine: Current knowledge and future directions

2023

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Background Epigenetic mechanisms, including DNA methylation, microRNAs and histone modifications, may modulate the genetic expression in migraine and its interaction with internal and external factors, such as lifestyle and environmental changes. Objective To summarize, contextualize and critically analyze the published literature on the current state of epigenetic mechanisms in migraine in a narrative review. Findings The studies published to date have used different approaches and methodologies to determine the role of epigenetic mechanisms in migraine. Epigenetic changes seem to be involved in migraine and are increasing our knowledge of the disease. Conclusions Changes in DNA methylation, microRNA expression and histone modifications could be utilized as biomarkers that would be highly valuable for patient stratification, molecular diagnosis, and precision medicine in migraine.

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“…Recently, Rubino et al analyzed two CpG islands in the CALCA gene: one located in the distal promoter between −2762 and −2362 bp and the other situated in the proximal promoter between −1662 and −1028 bp ( Figure 6 ) in DNA isolated from whole-blood samples obtained from individuals with episodic migraine without aura and healthy controls [ 65 ]. They found hypomethylation of two CpG dinucleotides within the proximal region located at −1461 and −1415 in migraine patients compared with controls.…”

Section: Epigenetic Connections Of Cgrpmentioning

confidence: 99%

“…The CpG sites within either island are only symbolically marked by short vertical bars. Positions of two CpG sites located at −1461 and −1415 and recently identified as hypomethylated in migraine patients by Rubino et al [ 65 ] are also presented.…”

Section: Figurementioning

confidence: 99%

Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine

Fila

Sobczuk

Pawłowska

et al. 2022

IJMS

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The calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of several pain-related syndromes, including migraine. Targeting CGRP and its receptor by their antagonists and antibodies was a breakthrough in migraine therapy, but the need to improve efficacy and limit the side effects of these drugs justify further studies on the regulation of CGRP in migraine. The expression of the CGRP encoding gene, CALCA, is modulated by epigenetic modifications, including the DNA methylation, histone modification, and effects of micro RNAs (miRNAs), circular RNAs, and long-coding RNAs (lncRNAs). On the other hand, CGRP can change the epigenetic profile of neuronal and glial cells. The promoter of the CALCA gene has two CpG islands that may be specifically methylated in migraine patients. DNA methylation and lncRNAs were shown to play a role in the cell-specific alternative splicing of the CALCA primary transcript. CGRP may be involved in changes in neural cytoarchitecture that are controlled by histone deacetylase 6 (HDAC6) and can be related to migraine. Inhibition of HDAC6 results in reduced cortical-spreading depression and a blockade of the CGRP receptor. CGRP levels are associated with the expression of several miRNAs in plasma, making them useful peripheral markers of migraine. The fundamental role of CGRP in inflammatory pain transmission may be epigenetically regulated. In conclusion, epigenetic connections of CGRP should be further explored for efficient and safe antimigraine therapy.

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Analysis of the DNA methylation pattern of the promoter region of calcitonin gene-related peptide 1 gene in patients with episodic migraine: An exploratory case-control study

Cited by 12 publications

References 32 publications

DNA methylation status of interspersed repetitive sequences in patients with migraine

DNA methylation status of interspersed repetitive sequences in patients with migraine

The impact of epigenetic mechanisms in migraine: Current knowledge and future directions

Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine

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