Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine

Neurology. 2019 Apr 16;92(16):e1899-e1911. doi: 10.1212/WNL.0000000000007313. Epub 2019 Apr 3.

Abstract

Objective: To identify a plasma metabolomic biomarker signature for migraine.

Methods: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses.

Results: Decreases in the level of apolipoprotein A1 (β -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status.

Conclusions: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cohort Studies
  • Fatty Acids, Omega-3 / blood
  • Female
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Male
  • Metabolome
  • Metabolomics
  • Middle Aged
  • Migraine Disorders / blood*
  • Nuclear Magnetic Resonance, Biomolecular
  • Proton Magnetic Resonance Spectroscopy
  • Sex Factors

Substances

  • Biomarkers
  • Fatty Acids, Omega-3
  • Lipoproteins, HDL