A prospective study of serum metabolites and risk of ischemic stroke.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
16 04 2019
Historique:
received: 20 10 2017
accepted: 19 12 2018
pubmed: 15 3 2019
medline: 8 1 2020
entrez: 15 3 2019
Statut: ppublish

Résumé

To identify promising blood-based biomarkers and novel etiologic pathways of disease risk, we applied an untargeted serum metabolomics profiling in a community-based prospective study of ischemic stroke (IS). In 3,904 men and women from the Atherosclerosis Risk In Communities study, Cox proportional hazard models were used to estimate the association of incident IS with the standardized level of 245 fasting serum metabolites individually, adjusting for age, sex, race, field center, batch, diabetes, hypertension, current smoking status, body mass index, and estimated glomerular filtration rate. Validation of results was carried out in an independent sample of 114 IS cases and 112 healthy controls. Serum levels of 2 long-chain dicarboxylic acids, tetradecanedioate and hexadecanedioate, were strongly correlated ( Two serum long-chain dicarboxylic acids, metabolic products of ω-oxidation of fatty acids, were associated with IS and CES independently of known risk factors. Pathways related to intracellular hexadecanedioate synthesis or those involved in its clearance from the circulation may mediate IS risk. These results highlight the potential of metabolomics to discover novel circulating biomarkers for stroke and to unravel novel pathways for IS and its subtypes.

Identifiants

pubmed: 30867269
pii: WNL.0000000000007279
doi: 10.1212/WNL.0000000000007279
pmc: PMC6550501
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1890-e1898

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS087541
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052409
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Daokun Sun (D)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Steffen Tiedt (S)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Bing Yu (B)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Xueqiu Jian (X)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Rebecca F Gottesman (RF)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Thomas H Mosley (TH)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Eric Boerwinkle (E)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Martin Dichgans (M)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Myriam Fornage (M)

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany. Myriam.Fornage@uth.tmc.edu.

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