Metabolomic profiling identifies novel associations with electrolyte and acid-base homeostatic patterns

Menni, C. et al. (2019) Metabolomic profiling identifies novel associations with electrolyte and acid-base homeostatic patterns. Scientific Reports, 9, 15088. (doi: 10.1038/s41598-019-51492-3) (PMID:31636301) (PMCID:PMC6803625)

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Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10 ), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.

Item Type:Articles
Additional Information:This work was supported by the MRC AimHy (MR/M016560/1) project grant, by the Wellcome trust programme grant HATS (Genetics of ageing: The genetic and environmental determinants of ageing in women), project No 081878/Z/06/Z and by the CDRF. Twins UK receives funding from the Wellcome Trust European Community’s Seventh Framework Programme (FP7/2007-2013 to TwinsUK); the National Institute for Health Research (NIHR) Clinical Research Facility at Guy’s & St Thomas’ NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. HLI collaborated with KCL to produce the metabolomics data from Metabolon Inc. S.P. is funded by the Medical Research Council (MR/M016560/1 and The AIM-HY Study) and the British Heart Foundation (PG/12/85/29925 and CS/16/1/31878). L.M. is funded by a BHF fellowship (FS/14/52/30901). SHIP is funded by the German Federal Ministry of Education and Research (BMBF, grants 01ZZ96030 and 01ZZ0701), the Ministry of Education, Research and Cultural Affairs as well as the Ministry of Social Affairs of the Federal State of Mecklenburg-West Pomerania. K.S. was supported by the ‘Biomedical Research Program’ funds at Weill Cornell Medicine in Qatar, a program funded by the Qatar Foundation.
Glasgow Author(s) Enlighten ID:Aman, Alisha and Padmanabhan, Professor Sandosh and McCallum, Dr Linsay
Authors: Menni, C., McCallum, L., Pietzner, M., Zierer, J., Aman, A., Suhre, K., Mohney, R. P., Mangino, M., Friedrich, N., Spector, T. D., and Padmanabhan, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Scientific Reports 9:15088
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
167816Genetic, molecular and functional dissection of a novel pathway for hypertension: Uromodulin, renal function, sodium homeostasis and blood pressure.Sandosh PadmanabhanBritish Heart Foundation (BHF)PG/12/85/29925Institute of Cardiovascular & Medical Sciences
190795Serum Chloride - epidemiology and genetic dissection of a novel marker of cardiovascular riskSandosh PadmanabhanBritish Heart Foundation (BHF)FS/14/52/30901Institute of Cardiovascular & Medical Sciences
676621Ancestry and biological informative markers for stratification of hypertension - The AIM HY studySandosh PadmanabhanMedical Research Council (MRC)MR/M016560/1RI CARDIOVASCULAR & MEDICAL SCIENCES