Metabolomic profiling identifies novel associations with Electrolyte and Acid-Base Homeostatic patterns

Cristina Menni, Linsay McCallum, Maik Pietzner, Jonas Zierer, Alisha Aman, Karsten Suhre, Robert P. Mohney, Massimo Mangino, Nele Friedrich, Tim D. Spector, Sandosh Padmanabhan

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Abstract

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 × 10−5), 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.

Original languageEnglish
Article number15088
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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Menni, C., McCallum, L., Pietzner, M., Zierer, J., Aman, A., Suhre, K., Mohney, R. P., Mangino, M., Friedrich, N., Spector, T. D., & Padmanabhan, S. (2019). Metabolomic profiling identifies novel associations with Electrolyte and Acid-Base Homeostatic patterns. Scientific reports, 9(1), [15088]. https://doi.org/10.1038/s41598-019-51492-3