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

• Published in: European journal of pharmaceutical sciences Vol. 131; pp. 93 - 98
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2019
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adult; Antihypertensive Agents - pharmacology; Antihypertensive response; Atenolol - pharmacology; Beta-blocker; Biomarker; Female; Humans; Hypertension; Hypertension - blood; Hypertension - genetics; Male; Metoprolol - pharmacology; microRNA; MicroRNAs - blood; Middle Aged; Antihypertensive response; Hypertension; microRNA; Biomarker; Beta-blocker
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2019.02.013

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. [Display omitted]