TY - JOUR
T1 - Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies
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.
N1 - Funding Information:
This study was ancillary to the PEAR study that was supported by the National Institutes of Health grant ( U01 GM074492 ) as part of the NIH Pharmacogenomics Research Network and the National Center for Advancing Translational Sciences under the award numbers UL1 TR000064 ( University of Florida ), UL1 TR000454 ( Emory University ), and UL1 TR000135 ( Mayo Clinic ). PEAR-2 was supported by funds from the Mayo Foundation . This study was also supported by the funding from the Embassy of the Arab Republic of Egypt to M. Solayman.
Funding Information:
This study was ancillary to the PEAR study that was supported by the National Institutes of Health grant (U01 GM074492) as part of the NIH Pharmacogenomics Research Network and the National Center for Advancing Translational Sciences under the award numbers UL1 TR000064 (University of Florida), UL1 TR000454 (Emory University), and UL1 TR000135 (Mayo Clinic). PEAR-2 was supported by funds from the Mayo Foundation. This study was also supported by the funding from the Embassy of the Arab Republic of Egypt to M. Solayman.
Publisher Copyright:
© 2019
PY - 2019/4/1
Y1 - 2019/4/1
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.
KW - Antihypertensive response
KW - Beta-blocker
KW - Biomarker
KW - Hypertension
KW - microRNA
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UR - http://www.scopus.com/inward/citedby.url?scp=85061380862&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2019.02.013
DO - 10.1016/j.ejps.2019.02.013
M3 - Article
C2 - 30753892
AN - SCOPUS:85061380862
VL - 131
SP - 93
EP - 98
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
ER -