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DNA-methylation and immunological response in medication overuse headache
Louise Ninett Carlsen1, Christine Søholm Hansen2, Lisette J A Kogelman1
1Danish Headache Center, Rigshospitalet, Denmark.
Cephalalgia : an International Journal of Headache
|February 14, 2023
Summary
Medication-overuse headache patients show increased immune response and differential DNA methylation. This immune response decreased with fewer headache days, suggesting potential biomarkers for treatment response.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Medication-overuse headache (MOH) is a common neurological disorder.
- The underlying biological mechanisms of MOH, particularly epigenetic factors, remain underexplored.
Purpose of the Study:
- To investigate differential DNA methylation patterns in medication-overuse headache patients.
- To explore the association between DNA methylation, immunological response, and headache reduction in MOH.
Main Methods:
- A cross-sectional case-control pilot study involving 120 MOH patients and 57 controls.
- Longitudinal analysis of 100 MOH patients over six months, assessing blood cell proportions and DNA methylation.
- Epigenome-wide association study (EWAS) comparing MOH patients to controls and analyzing longitudinal methylation changes.
Main Results:
- MOH patients exhibited a higher neutrophile-lymphocyte ratio, indicating increased immunological response (FDR <0.001).
- Reduced headache frequency was associated with a lower neutrophile-lymphocyte ratio (FDR = 0.041).
- Three genes (CORIN, CCKBR, CLDN9) were hypermethylated in specific cell types in MOH patients.
Conclusions:
- The study supports a heightened immunological response in MOH patients, which diminishes with headache reduction.
- Differential methylation was observed in innate immune cells of MOH patients, but no longitudinal methylation changes correlated with headache reduction.
- Findings generate hypotheses for future biomarker discovery in medication-overuse headache.
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