Division of Cardiovascular Medicine (J.B.H.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Division of Genetic Medicine (A.G.B.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Circ Res. 2022 Jan 7;130(1):149-161. doi: 10.1161/CIRCRESAHA.121.319809.
Advances in population-scale genomic sequencing have greatly expanded the understanding of the inherited basis of cardiovascular disease (CVD). Reanalysis of these genomic datasets identified an unexpected risk factor for CVD, somatically acquired DNA mutations. In this review, we provide an overview of somatic mutations and their contributions to CVD. We focus on the most common and well-described manifestation, clonal hematopoiesis of indeterminate potential. We also review the currently available data regarding how somatic mutations lead to tissue mosaicism in various forms of CVD, including atrial fibrillation and aortic aneurism associated with Marfan Syndrome. Finally, we highlight future research directions given current knowledge gaps and consider how technological advances will enhance the discovery of somatic mutations in CVD and management of patients with somatic mutations.
人口规模基因组测序的进展极大地扩展了人们对心血管疾病 (CVD) 遗传基础的理解。对这些基因组数据集的重新分析确定了 CVD 的一个意外风险因素，即体细胞获得性 DNA 突变。在这篇综述中，我们提供了体细胞突变及其对 CVD 贡献的概述。我们重点介绍最常见和描述最详细的表现形式，即不确定潜能的克隆性造血。我们还回顾了目前关于体细胞突变如何导致各种形式的 CVD 组织嵌合体的现有数据，包括与马凡综合征相关的心房颤动和主动脉瘤。最后，鉴于当前的知识空白，我们强调了未来的研究方向，并考虑了技术进步将如何增强 CVD 中体细胞突变的发现以及体细胞突变患者的管理。
