罕见变异遗传和扩展性心肌病严重程度:DCM精准医学研究
Mark Hofmeyer1, Garrie J Haas2,3,4, Elizabeth Jordan2,5
1MedStar Health Research Institute, Medstar Washington Hospital Center, Washington, DC (M.H.).
Circulation
|August 29, 2023
概括
高度扩张性心肌病 (DCM) 与罕见遗传变异的可能性更高. 这一发现有助于评估DCM患者及其家属的结果.
科学领域:
- 心血管遗传学
- 精准医学
- 基因组医学
背景情况:
- 扩张性心肌病是一种遗传性心脏病.
- 先进的DCM需要先进的治疗,如左心室辅助装置 (LVAD) 或心脏移植 (HT).
- 已知DCM的遗传基础,但与晚期疾病的联系仍未得到充分研究.
研究的目的:
- 研究罕见遗传变异与晚期扩张性心肌病 (DCM) 之间的关联.
- 分析多样化的基因数据以了解DCM的严重程度.
- 确定需要LVAD/HT的高级DCM的潜在遗传风险因素.
主要方法:
- 在美国DCM精准医学研究 (2016-2021) 中分析了1198名患者的临床和遗传数据.
- 将DCM的严重程度分为高级 (LVAD/HT),中度 (仅ICD) 和轻度 (没有).
- 评估了36个DCM基因的罕见变异,控制了人口,生活方式和并发症因素.
主要成果:
- 26. 2% 的 LVAD/ HT 患者具有致病性/ 可能致病性变体,而仅有 15. 9% (仅有 ICD) 和 15. 0% (均不存在).
- 在调整后,高级DCM患者患有致病/ 致病可能性较高的罕见变体 (OR 2. 3; 95% CI 1. 5- 3. 6).
- 基因发现与祖先或仅使用ICD和不使用ICD组之间没有显著差异.
结论:
- 先进的DCM与DCM基因中致病性/可能致病性罕见变异的更高流行率有关.
- 这些遗传发现可能会改善DCM患者的风险分层.
- 了解遗传联系可以帮助DCM患者及其家属制定治疗策略.
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