{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:26:33Z","timestamp":1777623993500,"version":"3.51.4"},"reference-count":42,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether medication-overuse headache patients have differential DNA-methylation pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected blood samples from 120 medication-overuse headache-patients, 57 controls (29 episodic migraine patients and 28 healthy controls) in a hypothesis-generating cross-sectional case-control pilot study; 100 of the medication-overuse headache-patients were followed for six months and samples were collected at two and six months for the longitudinal methylation analyses. Blood cell proportions of leucocytes (neutrophils, NK-cells, monocytes, CD8+ and CD4+ T-cells, and B-cells) and the neutrophile-lymphocyte ratio were estimated using methylation data as a measure for immunological analysis and a cell type-specific epigenome wide association study was conducted between medication-overuse headache-patients and controls, and longitudinally for reduction in headache days\/month among medication-overuse headache-patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found a higher neutrophile-lymphocyte ratio in medication-overuse headache-patients compared to controls, indicating a higher immunological response in medication-overuse headache-patients (false discovery rate (adjusted p-value)&lt;0.001). Reduction in headache days\/month (9.8; 95% CI 8.1\u201311.5) was associated with lower neutrophile-lymphocyte ratio (false discovery rate adjusted p-value\u2009=\u20090.041). Three genes ( CORIN, CCKBR and CLDN9) were hypermethylated in specific cell types in medication-overuse headache-patients compared to controls. No methylation differences were associated with reduction in headache days in medication-overuse headache-patients after six months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This pilot study was consistent with higher immunological response in medication-overuse headache-patients which decreased with a reduction in headache days in longitudinal analysis. medication-overuse headache-patients exhibited differential methylation in innate immune cells but did not exhibit longitudinal differences with alterations in headache days. Our study creates hypotheses for further biomarker searches. ClinicalTrials.gov Identifier: NCT02993289<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024221147482","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T06:20:43Z","timestamp":1676355643000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["DNA-methylation and immunological response in medication overuse headache"],"prefix":"10.1177","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3634-7287","authenticated-orcid":false,"given":"Louise Ninett","family":"Carlsen","sequence":"first","affiliation":[{"name":"Danish Headache Center, Rigshospitalet, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine S\u00f8holm","family":"Hansen","sequence":"additional","affiliation":[{"name":"Statens Serum Institute, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9782-7810","authenticated-orcid":false,"given":"Lisette J. 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