Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension

Bliziotis, N. G. et al. (2022) Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension. Metabolites, 12(8), e679. (doi: 10.3390/metabo12080679) (PMID:35893246) (PMCID:PMC9394285)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was financially supported by ENSAT-HT, a project that has re- ceived funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 633983.
• Keywords: Confounders, metabolomics, multicenter, plasma NMR, preanalytical conditions.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Davies, Professor Eleanor and Van Kralingen, Ms Josie

Creator Roles

Van Kralingen, J.: Resources
Davies, E.: Resources

• Authors: Bliziotis, N. G., Kluijtmans, L. A.J., Tinnevelt, G. H., Reel, P., Reel, S., Langton, K., Robledo, M., Pamporaki, C., Pecori, A., Van Kralingen, J., Tetti, M., Engelke, U. F.H., Erlic, Z., Engel, J., Deutschbein, T., Nölting, S., Prejbisz, A., Richter, S., Adamski, J., Januszewicz, A., Ceccato, F., Scaroni, C., Dennedy, M. C., Williams, T. A., Lenzini, L., Gimenez-Roqueplo, A.-P., Davies, E., Fassnacht, M., Remde, H., Eisenhofer, G., Beuschlein, F., Kroiss, M., Jefferson, E., Zennaro, M.-C., Wevers, R. A., Jansen, J. J., Deinum, J., and Timmers, H. J.L.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Metabolites
• Publisher: MDPI
• ISSN: 2218-1989
• ISSN (Online): 2218-1989
• Published Online: 24 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Metabolites 12(8):e679
• Publisher Policy: Reproduced under a Creative Commons License