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

Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 2019;131():93-98

PMID: 30753892

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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.

Address: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.; Department of Medicine, The University of Chicago, Chicago, IL, USA.; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.; Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.; Division of Endocrinology, Diabetes and Nutrition, School of Medicine, University of Maryland Baltimore, MD, USA.; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.; Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA. Electronic address: [email protected].

DOI: 10.1016/j.ejps.2019.02.013

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MeSH Terms: Adrenergic beta-Antagonists, Adult, Antihypertensive Agents, Atenolol, Female, Humans, Hypertension, Male, Metoprolol, MicroRNAs, Middle Aged