Pharmacogenomic Effects of β-Blocker Use on Femoral Neck Bone Mineral Density
| Autor: | Melissa M. Formosa, Douglas P. Kiel, Nicholas R Fuggle, Nathalie van der Velde, Archana Nagarajan, Katerina Trajanoska, Leo D. Westbury, Bruno H. Stricker, Kathleen T. Nevola, Cyrus Cooper, Fernando Rivadeneira, Alexandra Hinton, Katherine J. Motyl, Christine W. Lary, Angela Xuereb-Anastasi, Elaine M. Dennison |
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| Přispěvatelé: | Geriatrics, AMS - Ageing & Vitality, APH - Aging & Later Life, Internal Medicine, Epidemiology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Oncology medicine.medical_specialty Adrenergic beta blockers Offspring Endocrinology Diabetes and Metabolism Context (language use) 030204 cardiovascular system & hematology bone 03 medical and health sciences Rotterdam Study 0302 clinical medicine Framingham Heart Study SDG 3 - Good Health and Well-being β-blocker Internal medicine genomics Medicine Clinical Research Articles miRNA Femoral neck pharmacogenomics Bone mineral business.industry musculoskeletal neural and ocular physiology MicroRNA Genomics musculoskeletal system beta blocker 030104 developmental biology medicine.anatomical_structure Cohort Pharmacogenomics Bone density business AcademicSubjects/MED00250 Cohort study |
| Zdroj: | Journal of the Endocrine Society Journal of the Endocrine Society, 5(8):bvab092. Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | CONTEXT: Recent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects. OBJECTIVE: To investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study’s (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study. METHODS: We used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD. RESULTS: One variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings. CONCLUSION: This analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures. peer-reviewed |
| Databáze: | OpenAIRE |
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