Pharmacometabolomic study of drug response to antihypertensive medications for hypertension marker identification in Han Chinese individuals in Taiwan

Yu Jen Liang, Kuang Mao Chiang, Li li Xiu, Chia Min Chung, Chi Jen Lo, Ming Shi Shiao, Mei Ling Cheng, Cheng Chin Kuo, Hsin Chou Yang*, Wen Harn Pan

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

Various groups of antihypertensive drugs targeting different pathways have been developed; however, the pharmacometabolic responses to these drugs have rarely been compared to elucidate the common pathway of blood pressure regulation. Here, we performed a comparative multi-dimensional pharmacometabolic study on the four major lines of antihypertensive drugs, namely angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics (DIURs), through ultra-performance liquid chromatography coupled to quantum time-of-flight mass spectrometry. Two hundred fifty patients with young-onset hypertension, who were equally divided among five study groups: non-medicated, ACEi, ARB, CCB, and DIUR groups, were recruited. In a metabolome-wide association study conducted through analysis of covariance, 37 molecular features significantly associated with pharmacometabolic responses to antihypertensive drugs were identified. One-third of these features were shared by multiple medications. ACEis, ARBs, and DIURs shared more features than CCB, partially reflecting that ACEis, ARBs, and DIURs affect the renin-angiotensin-aldosterone system. Thirteen molecular features were consistently identified by all four models of the analysis of covariance. A tandem mass spectrometry (or MS/MS) experiment was performed to decipher the chemical structure of these 13 molecular features, including ARB-associated lysophosphatidylcholine (P4135), CCB-associated diacylglycerol(15:0/18:2) (P1175), and DIUR-associated oleamide (P1516). In addition, diacylglycerol(15:0/14:2) (P408) was significantly associated with the pharmacometabolic response to all four antihypertensive drugs. The identified metabolites provide insights into the mechanisms of blood pressure regulation and potential predictive markers of pharmacometabolic responses to antihypertensive drugs.

Original languageEnglish
Pages (from-to)6458-6466
Number of pages9
JournalComputational and Structural Biotechnology Journal
Volume20
DOIs
StatePublished - 01 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

  • Antihypertensive drugs
  • Diacylglycerol
  • Liquid chromatography-mass spectrometry
  • Lysophosphatidylcholine
  • Oleamide
  • Pharmacometabolomics

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