Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension.

confounders metabolomics multicenter plasma NMR preanalytical conditions

Journal

Metabolites
ISSN: 2218-1989
Titre abrégé: Metabolites
Pays: Switzerland
ID NLM: 101578790

Informations de publication

Date de publication:
24 Jul 2022
Historique:
received: 30 05 2022
revised: 17 06 2022
accepted: 11 07 2022
entrez: 27 7 2022
pubmed: 28 7 2022
medline: 28 7 2022
Statut: epublish

Résumé

Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing's syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics. We compared unstratified samples of 106 PHT patients to 231 EHT patients, including 104 PA, 94 PPGL and 33 CS patients. Spectra were subjected to a multivariate statistical comparison of PHT to EHT forms and the associated signatures were obtained. Three approaches were applied to investigate and correct confounding effects. Though we found signatures that could separate PHT from EHT forms, there were also key similarities with the signatures of sample center of origin and sample age. The study design restricted the applicability of the corrections employed. With the samples that were available, no biomarkers for PHT vs. EHT could be identified. The complexity of the confounding effects, evidenced by their robustness to correction approaches, highlighted the need for a consensus on how to deal with variabilities probably attributed to preanalytical factors in retrospective, multicenter metabolomics studies.

Identifiants

pubmed: 35893246
pii: metabo12080679
doi: 10.3390/metabo12080679
pmc: PMC9394285
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : European Union
ID : 633983

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Auteurs

Nikolaos G Bliziotis (NG)

Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Leo A J Kluijtmans (LAJ)

Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Gerjen H Tinnevelt (GH)

Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, 6500 HB Nijmegen, The Netherlands.

Parminder Reel (P)

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK.

Smarti Reel (S)

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK.

Katharina Langton (K)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.

Mercedes Robledo (M)

Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.
Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy.

Christina Pamporaki (C)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.

Alessio Pecori (A)

Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy.

Josie Van Kralingen (J)

British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), Institute of Cardiovascular & Medical Sciences (ICAMS), University of Glasgow, Glasgow G12 8TA, UK.

Martina Tetti (M)

Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy.

Udo F H Engelke (UFH)

Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Zoran Erlic (Z)

Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Zurich, Switzerland.

Jasper Engel (J)

Biometris, Wageningen University & Research, 6708 PB Wageningen, The Netherlands.

Timo Deutschbein (T)

Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany.
Medicover Oldenburg MVZ, 26122 Oldenburg, Germany.

Svenja Nölting (S)

Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany.

Aleksander Prejbisz (A)

Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland.

Susan Richter (S)

Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307 Dresden, Germany.

Jerzy Adamski (J)

Research Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Center München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Institute of Experimental Genetics, Technical University München, 85350 Freising-Weihenstephan, Germany.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.

Andrzej Januszewicz (A)

Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland.

Filippo Ceccato (F)

Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy.

Carla Scaroni (C)

Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy.

Michael C Dennedy (MC)

The Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, H91 CF50 Galway, Ireland.

Tracy A Williams (TA)

Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy.

Livia Lenzini (L)

Department of Medicine-DIMED, Emergency and Hypertension Unit, University of Padova, University Hospital, 35126 Padova, Italy.

Anne-Paule Gimenez-Roqueplo (AP)

INSERM, PARCC, Université de Paris, 75015 Paris, France.
Service de Genétique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.

Eleanor Davies (E)

British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), Institute of Cardiovascular & Medical Sciences (ICAMS), University of Glasgow, Glasgow G12 8TA, UK.

Martin Fassnacht (M)

Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany.
Core Unit Clinical Mass Spectrometry, University Hospital Würzburg, 97080 Würzburg, Germany.
Comprehensive Cancer Center Mainfranken, Würzburg University, 97070 Würzburg, Germany.

Hanna Remde (H)

Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany.

Graeme Eisenhofer (G)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307 Dresden, Germany.

Felix Beuschlein (F)

Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Zurich, Switzerland.
Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany.

Matthias Kroiss (M)

Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany.
Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany.
Core Unit Clinical Mass Spectrometry, University Hospital Würzburg, 97080 Würzburg, Germany.
Comprehensive Cancer Center Mainfranken, Würzburg University, 97070 Würzburg, Germany.

Emily Jefferson (E)

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK.
Institute of Health & Wellbeing, Glasgow University, Glasgow G12 8RZ, UK.

Maria-Christina Zennaro (MC)

INSERM, PARCC, Université de Paris, 75015 Paris, France.
Service de Genétique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.

Ron A Wevers (RA)

Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Jeroen J Jansen (JJ)

Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, 6500 HB Nijmegen, The Netherlands.

Jaap Deinum (J)

Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Henri J L M Timmers (HJLM)

Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Classifications MeSH