Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies

Mohamed H. Solayman, Taimour Y. Langaee, Yan Gong, Mohamed H. Shahin, Stephen T Turner, Arlene B. Chapman, John G. Gums, Eric Boerwinkle, Amber L. Beitelshees, Manal El-Hamamsy, Lamia El-Wakeel, Rhonda M. Cooper-DeHoff, Osama A. Badary, Julie A. Johnson

Research output: Contribution to journalArticle

Abstract

β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and β-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate β1-adrenergic receptor and other β-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to β-blockers.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalEuropean Journal of Pharmaceutical Sciences
Volume131
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

Fingerprint

Pharmacogenetics
MicroRNAs
Antihypertensive Agents
Metoprolol
Atenolol
Biomarkers
Validation Studies
Adrenergic Receptors
Meta-Analysis
Logistic Models
Genes

Keywords

  • Antihypertensive response
  • Beta-blocker
  • Biomarker
  • Hypertension
  • microRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies. / Solayman, Mohamed H.; Langaee, Taimour Y.; Gong, Yan; Shahin, Mohamed H.; Turner, Stephen T; Chapman, Arlene B.; Gums, John G.; Boerwinkle, Eric; Beitelshees, Amber L.; El-Hamamsy, Manal; El-Wakeel, Lamia; Cooper-DeHoff, Rhonda M.; Badary, Osama A.; Johnson, Julie A.

In: European Journal of Pharmaceutical Sciences, Vol. 131, 01.04.2019, p. 93-98.

Research output: Contribution to journalArticle

Solayman, MH, Langaee, TY, Gong, Y, Shahin, MH, Turner, ST, Chapman, AB, Gums, JG, Boerwinkle, E, Beitelshees, AL, El-Hamamsy, M, El-Wakeel, L, Cooper-DeHoff, RM, Badary, OA & Johnson, JA 2019, 'Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies', European Journal of Pharmaceutical Sciences, vol. 131, pp. 93-98. https://doi.org/10.1016/j.ejps.2019.02.013
Solayman, Mohamed H. ; Langaee, Taimour Y. ; Gong, Yan ; Shahin, Mohamed H. ; Turner, Stephen T ; Chapman, Arlene B. ; Gums, John G. ; Boerwinkle, Eric ; Beitelshees, Amber L. ; El-Hamamsy, Manal ; El-Wakeel, Lamia ; Cooper-DeHoff, Rhonda M. ; Badary, Osama A. ; Johnson, Julie A. / Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies. In: European Journal of Pharmaceutical Sciences. 2019 ; Vol. 131. pp. 93-98.
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abstract = "β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and β-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate β1-adrenergic receptor and other β-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to β-blockers.",
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AU - Solayman, Mohamed H.

AU - Langaee, Taimour Y.

AU - Gong, Yan

AU - Shahin, Mohamed H.

AU - Turner, Stephen T

AU - Chapman, Arlene B.

AU - Gums, John G.

AU - Boerwinkle, Eric

AU - Beitelshees, Amber L.

AU - El-Hamamsy, Manal

AU - El-Wakeel, Lamia

AU - Cooper-DeHoff, Rhonda M.

AU - Badary, Osama A.

AU - Johnson, Julie A.

PY - 2019/4/1

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N2 - β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and β-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate β1-adrenergic receptor and other β-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to β-blockers.

AB - β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and β-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate β1-adrenergic receptor and other β-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to β-blockers.

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