From the Departments of Neurology (G.L.J.O., J.A.P., D.A.K., R.Z., I.d.B., M.D.F., G.M.T., A.M.J.M.v.d.M.), Human Genetics (A.D., L.S.V., P.A.C.'tH., A.M.J.M.v.d.M.), Molecular Epidemiology (M.B., P.E.S.), Radiology (D.A.K.), and Medical Statistics (J.J.G.), Leiden University Medical Centre; Department of Biological Psychology (L.L., R.P., D.I.B.), Vrije Universiteit Amsterdam; Amsterdam Public Health Institute (L.L.); Amsterdam Neuroscience and Amsterdam Public Health (M.B., C.S.T., Y.M., D.I.B., B.W.P.); Department of Psychiatry (M.B., C.S.T., Y.M., B.W.P.), VU University Medical Centre/GGZ inGeest, Amsterdam; Departments of Epidemiology (A.D., J.L., K.-x.W., N.A., M.A.I., C.M.v.D.) and Neurology (M.A.I.), Erasmus Medical Centre, Rotterdam; Departments of Genetics (J.F., L.F., C.W.) and Pediatrics (J.F.), University Medical Centre Groningen; Department of Internal Medicine (C.J.H.v.d.K., F.H.M.V., M.M.J.v.G., M.T.S., C.D.A.S.) and Heart and Vascular Center (M.T.S.), Maastricht University Medical Centre; CARIM School for Cardiovascular Diseases (C.J.H.v.d.K., M.M.J.v.G., I.C.W.A., M.T.S., P.C.D., C.D.A.S.), Department of Epidemiology (I.C.W.A.), MaCSBio Maastricht Centre for Systems Biology (I.C.W.A.), and Department of Epidemiology (P.C.D.), Maastricht University; Department of Radiology (M.A.I.), Erasmus MC University Medical Centre, Rotterdam; Leiden Academic Centre in Drug Research, Faculty Science (C.M.v.D.), Leiden University; and Centre for Molecular and Biomolecular Informatics (P.A.C.'tH.), Radboud University Medical Centre Nijmegen, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
Neurology. 2019 Apr 16;92(16):e1899-e1911. doi: 10.1212/WNL.0000000000007313. Epub 2019 Apr 3.
To identify a plasma metabolomic biomarker signature for migraine.
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.
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.
Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.
确定偏头痛的血浆代谢组学生物标志物特征。
在基于 H-NMR 的代谢组学平台上对来自 8 个荷兰队列（n=10153：2800 例偏头痛患者和 7353 例对照）的血浆样本进行分析，以定量测定 146 种个体代谢物（如脂质、脂肪酸和脂蛋白）和 79 种代谢物比值。采用单代谢物逻辑回归结合非分层和性别分层的随机效应荟萃分析，获得与偏头痛相关的代谢物测量值。然后进行全局检验分析，以确定与偏头痛相关的相关代谢物集合。在单代谢物和全局检验分析中应用 Holm 程序将组间错误率控制在 5%。
小高密度脂蛋白亚类（HDL）中载脂蛋白 A1 水平降低（β=-0.10；95%置信区间 [CI] -0.16，-0.05；调整后 =0.029）和小 HDL 中游离胆固醇与总脂质比值降低（β=-0.10；95% CI -0.15，-0.05；调整后 =0.029）与偏头痛状态相关。此外，仅在男性参与者中，ω-3 脂肪酸水平降低（β=-0.24；95% CI -0.36，-0.12；调整后 =0.033）与偏头痛相关。全局检验分析进一步表明，HDL 特征（而不是其他脂蛋白）与偏头痛状态相关。
血浆代谢组学分析显示偏头痛患者的 HDL 代谢发生改变，仅男性偏头痛患者的 ω-3 脂肪酸减少。
