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

Elisabeth Altmaier, Cristina Menni, Margit Heier, Christa Meisinger, Barbara Thorand, Jan Quell, Michael Kobl, Werner Römisch-Margl, Ana M. Valdes, Massimo Mangino, Melanie Waldenberger, Konstantin Strauch, Thomas Illig, Jerzy Adamski, Tim Spector, Christian Gieger, Karsten Suhre, Gabi Kastenmüller

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0153163
JournalPLoS One
Volume11
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Fingerprint

pharmacogenomics
Enzyme inhibition
Metabolomics
enzyme inhibition
Pharmacogenetics
peptidyl-dipeptidase A
metabolomics
Peptidyl-Dipeptidase A
Dipeptides
dipeptides
Population
Enzyme activity
Angiotensin-Converting Enzyme Inhibitors
enzyme inhibitors
Oligopeptides
Homozygote
Metabolites
phenylalanylserine
oligopeptides
aspartyl-phenylalanine

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Altmaier, E., Menni, C., Heier, M., Meisinger, C., Thorand, B., Quell, J., ... Kastenmüller, G. (2016). The pharmacogenetic footprint of ACE inhibition: A population-based metabolomics study. PLoS One, 11(4), [e0153163]. https://doi.org/10.1371/journal.pone.0153163

The pharmacogenetic footprint of ACE inhibition : A population-based metabolomics study. / Altmaier, Elisabeth; Menni, Cristina; Heier, Margit; Meisinger, Christa; Thorand, Barbara; Quell, Jan; Kobl, Michael; Römisch-Margl, Werner; Valdes, Ana M.; Mangino, Massimo; Waldenberger, Melanie; Strauch, Konstantin; Illig, Thomas; Adamski, Jerzy; Spector, Tim; Gieger, Christian; Suhre, Karsten; Kastenmüller, Gabi.

In: PLoS One, Vol. 11, No. 4, e0153163, 01.04.2016.

Research output: Contribution to journalArticle

Altmaier, E, Menni, C, Heier, M, Meisinger, C, Thorand, B, Quell, J, Kobl, M, Römisch-Margl, W, Valdes, AM, Mangino, M, Waldenberger, M, Strauch, K, Illig, T, Adamski, J, Spector, T, Gieger, C, Suhre, K & Kastenmüller, G 2016, 'The pharmacogenetic footprint of ACE inhibition: A population-based metabolomics study', PLoS One, vol. 11, no. 4, e0153163. https://doi.org/10.1371/journal.pone.0153163
Altmaier E, Menni C, Heier M, Meisinger C, Thorand B, Quell J et al. The pharmacogenetic footprint of ACE inhibition: A population-based metabolomics study. PLoS One. 2016 Apr 1;11(4). e0153163. https://doi.org/10.1371/journal.pone.0153163
Altmaier, Elisabeth ; Menni, Cristina ; Heier, Margit ; Meisinger, Christa ; Thorand, Barbara ; Quell, Jan ; Kobl, Michael ; Römisch-Margl, Werner ; Valdes, Ana M. ; Mangino, Massimo ; Waldenberger, Melanie ; Strauch, Konstantin ; Illig, Thomas ; Adamski, Jerzy ; Spector, Tim ; Gieger, Christian ; Suhre, Karsten ; Kastenmüller, Gabi. / The pharmacogenetic footprint of ACE inhibition : A population-based metabolomics study. In: PLoS One. 2016 ; Vol. 11, No. 4.
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