Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. (16th April 2019)

• Record Type: Journal Article
• Authors: Onderwater, Gerrit L.J.; Ligthart, Lannie; Bot, Mariska; Demirkan, Ayse; Fu, Jingyuan; van der Kallen, Carla J.H.; Vijfhuizen, Lisanne S.; Pool, René; Liu, Jun; Vanmolkot, Floris H.M.; Beekman, Marian; Wen, Ke-xin; Amin, Najaf; Thesing, Carisha S.; Pijpers, Judith A.; Kies, Dennis A.; Zielman, Ronald; de Boer, Irene; van Greevenbroek, Marleen M.J.; Arts, Ilja C.W.; Milaneschi, Yuri; Schram, Miranda T.; Dagnelie, Pieter C.; Franke, Lude; Ikram, M. Arfan; Ferrari, Michel D.; Goeman, Jelle J.; Slagboom, P. Eline; Wijmenga, Cisca; Stehouwer, Coen D.A.; Boomsma, Dorret I.; van Duijn, Cornelia M.; Penninx, Brenda W.; 't Hoen, Peter A.C.; Terwindt, Gisela M.; van den Maagdenberg, Arn M.J.M.;
• Is Part Of: Neurology. Volume 92:Number 16(2019)
• Publication Date: 2019-04-16
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000007313
• Languages: English
• ISSNs: 0028-3878

Abstract

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 1 H-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.