DNA-methylation and immunological response in medication overuse headache

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Cephalalgia, Vol. 43, No. 3, 2023, p. 1-11.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Carlsen, LN, Hansen, CS, Kogelman, LJA, Werge, TM, Ullum, H, Bybjerg-Grauholm, J, Hansen, TF & Jensen, RH 2023, 'DNA-methylation and immunological response in medication overuse headache', Cephalalgia, vol. 43, no. 3, pp. 1-11. https://doi.org/10.1177/03331024221147482

APA

Carlsen, L. N., Hansen, C. S., Kogelman, L. J. A., Werge, T. M., Ullum, H., Bybjerg-Grauholm, J., Hansen, T. F., & Jensen, R. H. (2023). DNA-methylation and immunological response in medication overuse headache. Cephalalgia, 43(3), 1-11. https://doi.org/10.1177/03331024221147482

Vancouver

Carlsen LN, Hansen CS, Kogelman LJA, Werge TM, Ullum H, Bybjerg-Grauholm J et al. DNA-methylation and immunological response in medication overuse headache. Cephalalgia. 2023;43(3):1-11. https://doi.org/10.1177/03331024221147482

Author

Carlsen, Louise Ninett ; Hansen, Christine Søholm ; Kogelman, Lisette J.A. ; Werge, Thomas Mears ; Ullum, Henrik ; Bybjerg-Grauholm, Jonas ; Hansen, Thomas Folkmann ; Jensen, Rigmor Højland. / DNA-methylation and immunological response in medication overuse headache. In: Cephalalgia. 2023 ; Vol. 43, No. 3. pp. 1-11.

Bibtex

@article{3271df53f6cc48b7abff1a2ef74bbae5,
title = "DNA-methylation and immunological response in medication overuse headache",
abstract = "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.",
keywords = "Biomarkers, chronic headache, overuse of analgesics",
author = "Carlsen, {Louise Ninett} and Hansen, {Christine S{\o}holm} and Kogelman, {Lisette J.A.} and Werge, {Thomas Mears} and Henrik Ullum and Jonas Bybjerg-Grauholm and Hansen, {Thomas Folkmann} and Jensen, {Rigmor H{\o}jland}",
year = "2023",
doi = "10.1177/03331024221147482",
language = "English",
volume = "43",
pages = "1--11",
journal = "Cephalalgia",
issn = "0800-1952",
publisher = "SAGE Publications",
number = "3",

}

RIS

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