Large-scale Plasma Metabolome Analysis Reveals Alterations in HDL Metabolism in Migraine

Overview

Journal Neurology

Specialty Neurology

Date 2019 Apr 5

PMID 30944236

Citations 27

Authors

Gerrit L J Onderwater

Lannie Ligthart

Mariska Bot

Ayse Demirkan

Jingyuan Fu

Carla J H van der Kallen

Lisanne S Vijfhuizen

Rene Pool

Jun Liu

Floris H M Vanmolkot

Marian Beekman

Ke-Xin Wen

Najaf Amin

Carisha S Thesing

Judith A Pijpers

Dennis A Kies

Ronald Zielman

Irene de Boer

Marleen M J van Greevenbroek

Ilja C W Arts

Yuri Milaneschi

Miranda T Schram

Pieter C Dagnelie

Lude Franke

M Arfan Ikram

Michel D Ferrari

Jelle J Goeman

P Eline Slagboom

Cisca Wijmenga

Coen D A Stehouwer

Dorret I Boomsma

Cornelia M Van Duijn

Brenda W Penninx

Peter A C t Hoen

Gisela M Terwindt

Arn M J M van den Maagdenberg

Affiliations

Soon will be listed here.

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 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 = 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 = 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 = 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.

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