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

Autor: Bliziotis NG; Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Kluijtmans LAJ; Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Tinnevelt GH; Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, 6500 HB Nijmegen, The Netherlands., Reel P; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK., Reel S; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK., Langton K; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., 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., Pamporaki C; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., Pecori A; Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy., 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., Tetti M; Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy., Engelke UFH; Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Erlic Z; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Zurich, Switzerland., Engel J; Biometris, Wageningen University & Research, 6708 PB Wageningen, The Netherlands., 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., Nölting S; Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany., Prejbisz A; Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland., Richter S; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, 01307 Dresden, Germany., 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., Januszewicz A; Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland., Ceccato F; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy., Scaroni C; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy., Dennedy MC; The Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, H91 CF50 Galway, Ireland., Williams TA; Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Torino, 10124 Torino, Italy., Lenzini L; Department of Medicine-DIMED, Emergency and Hypertension Unit, University of Padova, University Hospital, 35126 Padova, Italy., 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., Davies E; British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), Institute of Cardiovascular & Medical Sciences (ICAMS), University of Glasgow, Glasgow G12 8TA, UK., 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., Remde H; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany., 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., 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., 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., 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., 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., Wevers RA; Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Jansen JJ; Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, 6500 HB Nijmegen, The Netherlands., Deinum J; Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Timmers HJLM; Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Metabolites [Metabolites] 2022 Jul 24; Vol. 12 (8). Date of Electronic Publication: 2022 Jul 24.
DOI: 10.3390/metabo12080679
Abstrakt: 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.
Databáze: MEDLINE