贝塔抑制剂在骨上使用的药物遗传学和微RNA机制
Christine W Lary1,2, Elizabeth J Atkinson3, Jennifer Spillane1
1Roux Institute at Northeastern University, Department of Public Health and Health Sciences, Portland, ME 04101, United States.
概括
贝塔抑制剂 (BBs) 可能改善骨健康. 这项研究发现了与BB对骨矿物质密度 (BMD) 和骨周转标记 (BTM) 的影响相关的遗传变异和microRNAs (miRNAs),这表明了个性化治疗的潜力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 遗传学 是一个遗传学.
- 骨生物学 骨生物学 骨生物学
背景情况:
- 以前的研究表明,使用β阻塞剂 (BB) 与改善骨健康之间存在联系.
- 涉及β上腺素受体基因的药物遗传和微RNA (miRNA) 介导机制.
研究的目的:
- 验证药物遗传效应并发现与BBs对骨的影响相关的新型miRNA候选者.
- 为了研究使用BBs的绝经后妇女的骨周转标记 (BTM) 和骨矿物密度 (BMD) 的变化.
主要方法:
- 一项试点随机试验的辅助研究,涉及基因型和miRNA测序.
- 在基线和20周对阿提诺洛尔或安慰剂组的24名参与者的分析.
- 心血管特征反应与骨再吸收标记反应的比较.
主要成果:
- 鉴定了ADRB1,ADRB2和HDAC4变异对BMD和BTM的显著药物遗传效应.
- 在低响应者中观察到miR-19a-3p随着时间的推移与atenolol的治疗效果.
- 与高响应者和安慰剂相比,在低响应者中发现了许多miRNAs的上调.
结论:
- 遗传变异和特定的miRNA在对β阻断剂的骨反应中起作用.
- 阿提诺洛尔的心血管作用似乎在很大程度上独立于其对骨再吸收的影响.
- 研究结果支持针对骨健康的BB治疗的个性化治疗方法.
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