{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T01:22:25Z","timestamp":1774401745843,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cooperation Programme Interreg V-A Spain\u2013Portugal","award":["0702_MIGRAINEE_2_E"],"award-info":[{"award-number":["0702_MIGRAINEE_2_E"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MEC-NEU\/29486\/2017"],"award-info":[{"award-number":["PTDC\/MEC-NEU\/29486\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Migraine is a complex neurovascular disorder affecting one billion people worldwide, mainly females. It is characterized by attacks of moderate to severe headache pain, with associated symptoms. Receptor activity modifying protein (RAMP1) is part of the Calcitonin Gene-Related Peptide (CGRP) receptor, a pharmacological target for migraine. Epigenetic processes, such as DNA methylation, play a role in clinical presentation of various diseases. DNA methylation occurs mostly in the gene promoter and can control gene expression. We investigated the methylation state of the RAMP1 promoter in 104 female blood DNA samples: 54 migraineurs and 50 controls. We treated DNA with sodium bisulfite and performed PCR, Sanger Sequencing, and Epigenetic Sequencing Methylation (ESME) software analysis. We identified 51 CpG dinucleotides, and 5 showed methylation variability. Migraineurs had a higher number of individuals with all five CpG methylated when compared to controls (26% vs. 16%), although non-significant (p = 0.216). We also found that CpG \u2212284 bp, related to the transcription start site (TSS), showed higher methylation levels in cases (p = 0.011). This CpG may potentially play a role in migraine, affecting RAMP1 transcription or receptor malfunctioning and\/or altered CGRP binding. We hope to confirm this finding in a larger cohort and establish an epigenetic biomarker to predict female migraine risk.<\/jats:p>","DOI":"10.3390\/brainsci12050526","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A High Methylation Level of a Novel \u2212284 bp CpG Island in the RAMP1 Gene Promoter Is Potentially Associated with Migraine in Women"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-9501","authenticated-orcid":false,"given":"Estef\u00e2nia","family":"Carvalho","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1070-9606","authenticated-orcid":false,"given":"Andreia","family":"Dias","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alda","family":"Sousa","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Centre for Predictive and Preventive Genetics (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N\u00e1dia","family":"Pinto","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Centro de Matem\u00e1tica da Universidade do Porto (CMUP), 4169-007 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Lemos","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Alves-Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition","volume":"38","author":"Olesen","year":"2018","journal-title":"Cephalalgia Int. 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