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 language | English (US) |
|---|---|
| Pages (from-to) | 93-98 |
| Number of pages | 6 |
| Journal | European Journal of Pharmaceutical Sciences |
| Volume | 131 |
| DOIs | |
| State | Published - Apr 1 2019 |
| Externally published | Yes |
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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 journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=85061380862&partnerID=8YFLogxK
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 -