Pharmacogenetic and microRNA mechanisms of beta blocker use on bone.

Autor:	Lary CW; Roux Institute at Northeastern University.; MaineHealth Institute for Research, Scarborough, ME., Atkinson EJ; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN., Spillane J; Roux Institute at Northeastern University., Nayema Z; Roux Institute at Northeastern University., Roy TA; MaineHealth Institute for Research, Scarborough, ME., Peters R; MaineHealth Institute for Research, Scarborough, ME.; University of Maine, Orono, ME., Scott GT; Roux Institute at Northeastern University., Chen H; Roux Institute at Northeastern University., Nagarajan A; Roux Institute at Northeastern University., Brown A; MaineHealth Institute for Research, Scarborough, ME., Motyl KJ; MaineHealth Institute for Research, Scarborough, ME.; University of Maine, Orono, ME.; Tufts University School of Medicine, Boston, MA., Monroe DG; Division of Endocrinology and Kogod Center on Aging, Mayo Clinic, Rochester, MN., Khosla S; Division of Endocrinology and Kogod Center on Aging, Mayo Clinic, Rochester, MN.
Jazyk:	angličtina
Zdroj:	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2024 Dec 13. Date of Electronic Publication: 2024 Dec 13.
DOI:	10.1093/jbmr/zjae200
Abstrakt:	Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial (RCT) was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/day), or nebivolol (5 mg/day) to determine changes in bone turnover markers (BTMs) and in bone mineral density (BMD) over 20 weeks. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial. We genotyped all participants and performed microRNA (miRNA) sequencing at baseline and at 20 weeks for 24 participants from the atenolol or placebo groups. We discovered several variants in ADRB1, ADRB2, and HDAC4 which showed significant pharmacogenetic effects with BMD at multiple sites and with BTMs. Our miRNA results showed a significant treatment effect for miR-19a-3p over time with atenolol use in the low-responder group compared to placebo. Overall, the longitudinal miRNA analysis showed a large number of miRNAs which were up-regulated over the trial in the low responders but not the high responders compared to placebo, of which miR-19a-3p was one example. Finally, we compared the response to atenolol treatment for cardiovascular traits (pulse, blood pressure) with the response for the bone resorption marker, CTX, and found a largely independent effect. Our results have implications for personalized therapy and for understanding mechanisms of BB treatment effect on bone. (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu