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Open Access 01-05-2014 | GENETIC EPIDEMIOLOGY

Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism

Authors: Elisabeth Altmaier, Gisela Fobo, Margit Heier, Barbara Thorand, Christine Meisinger, Werner Römisch-Margl, Melanie Waldenberger, Christian Gieger, Thomas Illig, Jerzy Adamski, Karsten Suhre, Gabi Kastenmüller

Published in: European Journal of Epidemiology | Issue 5/2014

Abstract

The mechanism of antihypertensive and lipid-lowering drugs on the human organism is still not fully understood. New insights on the drugs’ action can be provided by a metabolomics-driven approach, which offers a detailed view of the physiological state of an organism. Here, we report a metabolome-wide association study with 295 metabolites in human serum from 1,762 participants of the KORA F4 (Cooperative Health Research in the Region of Augsburg) study population. Our intent was to find variations of metabolite concentrations related to the intake of various drug classes and—based on the associations found—to generate new hypotheses about on-target as well as off-target effects of these drugs. In total, we found 41 significant associations for the drug classes investigated: For beta-blockers (11 associations), angiotensin-converting enzyme (ACE) inhibitors (four assoc.), diuretics (seven assoc.), statins (ten assoc.), and fibrates (nine assoc.) the top hits were pyroglutamine, phenylalanylphenylalanine, pseudouridine, 1-arachidonoylglycerophosphocholine, and 2-hydroxyisobutyrate, respectively. For beta-blockers we observed significant associations with metabolite concentrations that are indicative of drug side-effects, such as increased serotonin and decreased free fatty acid levels. Intake of ACE inhibitors and statins associated with metabolites that provide insight into the action of the drug itself on its target, such as an association of ACE inhibitors with des-Arg(9)-bradykinin and aspartylphenylalanine, a substrate and a product of the drug-inhibited ACE. The intake of statins which reduce blood cholesterol levels, resulted in changes in the concentration of metabolites of the biosynthesis as well as of the degradation of cholesterol. Fibrates showed the strongest association with 2-hydroxyisobutyrate which might be a breakdown product of fenofibrate and, thus, a possible marker for the degradation of this drug in the human organism. The analysis of diuretics showed a heterogeneous picture that is difficult to interpret. Taken together, our results provide a basis for a deeper functional understanding of the action and side-effects of antihypertensive and lipid-lowering drugs in the general population.

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Title: Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism
Authors: Elisabeth Altmaier
Gisela Fobo
Margit Heier
Barbara Thorand
Christine Meisinger
Werner Römisch-Margl
Melanie Waldenberger
Christian Gieger
Thomas Illig
Jerzy Adamski
Karsten Suhre
Gabi Kastenmüller
Publication date: 01-05-2014
Publisher: Springer Netherlands
Published in: European Journal of Epidemiology / Issue 5/2014
Print ISSN: 0393-2990
Electronic ISSN: 1573-7284
DOI: https://doi.org/10.1007/s10654-014-9910-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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