Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine.
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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, BBMRI Metabolomics Consortium
Аннотация
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.