DNA-methylation and immunological response in medication overuse headache
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DNA-methylation and immunological response in medication overuse headache. / Carlsen, Louise Ninett; Hansen, Christine Søholm; Kogelman, Lisette J.A.; Werge, Thomas Mears; Ullum, Henrik; Bybjerg-Grauholm, Jonas; Hansen, Thomas Folkmann; Jensen, Rigmor Højland.
I: Cephalalgia, Bind 43, Nr. 3, 2023, s. 1-11.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - DNA-methylation and immunological response in medication overuse headache
AU - Carlsen, Louise Ninett
AU - Hansen, Christine Søholm
AU - Kogelman, Lisette J.A.
AU - Werge, Thomas Mears
AU - Ullum, Henrik
AU - Bybjerg-Grauholm, Jonas
AU - Hansen, Thomas Folkmann
AU - Jensen, Rigmor Højland
PY - 2023
Y1 - 2023
N2 - OBJECTIVE: To investigate whether medication-overuse headache patients have differential DNA-methylation pattern. METHODS: 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. RESULTS: 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)<0.001). Reduction in headache days/month (9.8; 95% CI 8.1-11.5) was associated with lower neutrophile-lymphocyte ratio (false discovery rate adjusted p-value = 0.041).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. CONCLUSION: 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.
AB - OBJECTIVE: To investigate whether medication-overuse headache patients have differential DNA-methylation pattern. METHODS: 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. RESULTS: 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)<0.001). Reduction in headache days/month (9.8; 95% CI 8.1-11.5) was associated with lower neutrophile-lymphocyte ratio (false discovery rate adjusted p-value = 0.041).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. CONCLUSION: 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.
KW - Biomarkers
KW - chronic headache
KW - overuse of analgesics
U2 - 10.1177/03331024221147482
DO - 10.1177/03331024221147482
M3 - Journal article
C2 - 36786322
AN - SCOPUS:85148113824
VL - 43
SP - 1
EP - 11
JO - Cephalalgia
JF - Cephalalgia
SN - 0800-1952
IS - 3
ER -
ID: 337985004