{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:35:29Z","timestamp":1790728529334,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the GCSAML region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to GCSAML survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; GRM2 methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the GRM2 region were significantly associated with FM risk. Our study encourages better exploration of GCSAML and GRM2 functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.<\/jats:p>","DOI":"10.3390\/jcm10214992","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T23:24:42Z","timestamp":1635377082000},"page":"4992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["DNA Methylation Changes in Fibromyalgia Suggest the Role of the Immune-Inflammatory Response and Central Sensitization"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5096-2588","authenticated-orcid":false,"given":"Maria Carla","family":"Gerra","sequence":"first","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), SMI\u00ae, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7928-9956","authenticated-orcid":false,"given":"Davide","family":"Carnevali","sequence":"additional","affiliation":[{"name":"Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain"},{"name":"Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ossola","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-920X","authenticated-orcid":false,"given":"Alberto","family":"Gonz\u00e1lez-Villar","sequence":"additional","affiliation":[{"name":"Psychological Neuroscience Lab, Psychology Research Centre, School of Psychology, University of Minho, 4710-057 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-8040","authenticated-orcid":false,"given":"Inge S\u00f8kilde","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"},{"name":"Molecular Diagnostics, Aalborg University Hospital, 9100 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Tri\u00f1anes","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-2358","authenticated-orcid":false,"given":"Claudia","family":"Donnini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Manfredini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Arendt-Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), SMI\u00ae, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Carrillo-de-la-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/acr.20140","article-title":"The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity","volume":"62","author":"Wolfe","year":"2010","journal-title":"Arthritis Care Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.semarthrit.2016.08.012","article-title":"2016 Revisions to the 2010\/2011 fibromyalgia diagnostic criteria","volume":"46","author":"Wolfe","year":"2016","journal-title":"Semin. 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