TY - JOUR
T1 - Pharmacometabolomic study of drug response to antihypertensive medications for hypertension marker identification in Han Chinese individuals in Taiwan
AU - Liang, Yu Jen
AU - Chiang, Kuang Mao
AU - Xiu, Li li
AU - Chung, Chia Min
AU - Lo, Chi Jen
AU - Shiao, Ming Shi
AU - Cheng, Mei Ling
AU - Kuo, Cheng Chin
AU - Yang, Hsin Chou
AU - Pan, Wen Harn
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - Antihypertensive drugs
KW - Diacylglycerol
KW - Liquid chromatography-mass spectrometry
KW - Lysophosphatidylcholine
KW - Oleamide
KW - Pharmacometabolomics
UR - http://www.scopus.com/inward/record.url?scp=85142493796&partnerID=8YFLogxK
U2 - 10.1016/j.csbj.2022.11.030
DO - 10.1016/j.csbj.2022.11.030
M3 - 文章
AN - SCOPUS:85142493796
SN - 2001-0370
VL - 20
SP - 6458
EP - 6466
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
ER -