PuSH - Publication Server of Helmholtz Zentrum München

Altmaier, E. ; Menni, C.* ; Heier, M. ; Meisinger, C. ; Thorand, B. ; Quell, J. ; Kobl, M. ; Römisch-Margl, W. ; Valdes, A.M.* ; Mangino, M.* ; Waldenberger, M. ; Strauch, K. ; Illig, T. ; Adamski, J. ; Spector, T.* ; Gieger, C. ; Suhre, K. ; Kastenmüller, G.

The pharmacogenetic footprint of ACE inhibition: A population-based metabolomics study.

PLoS ONE 11:e0153163 (2016)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them-and perhaps also the other dipeptides-as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Angiotensin-converting Enzyme; Complement C3; Human Plasma; System; Hypertension; Association; Degradation; Hydrolysis; Activation; Peptides
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 11, Issue: 4, Pages: , Article Number: e0153163 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Bioinformatics and Systems Biology (IBIS)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)