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

ABSTRACT: ?-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to ?-blockers. Expression of 22 ?-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 ?-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate ?1-adrenergic receptor and other ?-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to ?-blockers.

SUBMITTER: Solayman MH 

PROVIDER: S-EPMC6467266 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature