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表观遗传学与心血管病精准医学:从基础概念到临床领域。

Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena.

机构信息

Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, Schlieren, Zurich, Switzerland.

Brigham and Women's Hospital, Division of Cardiovascular Medicine, Boston, MA, USA.

出版信息

Eur Heart J. 2018 Dec 14;39(47):4150-4158. doi: 10.1093/eurheartj/ehx568.

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and also inflict major burdens on morbidity, quality of life, and societal costs. Considering that CVD preventive medications improve vascular outcomes in less than half of patients (often relative risk reductions range from 12% to 20% compared with placebo), precision medicine offers an attractive approach to refine the targeting of CVD medications to responsive individuals in a population and thus allocate resources more wisely and effectively. New tools furnished by advances in basic science and translational medicine could help achieve this goal. This approach could reach beyond the practitioners 'eyeball' assessment or venerable markers derived from the physical examination and standard laboratory evaluation. Advances in genetics have identified novel pathways and targets that operate in numerous diseases, paving the way for 'precision medicine'. Yet the inherited genome determines only part of an individual's risk profile. Indeed, standard genomic approaches do not take into account the world of regulation of gene expression by modifications of the 'epi'genome. Epigenetic modifications defined as 'heritable changes to the genome that do not involve changes in DNA sequence' have emerged as a new layer of biological regulation in CVD and could advance individualized risk assessment as well as devising and deploying tailored therapies. This review, therefore, aims to acquaint the cardiovascular community with the rapidly advancing and evolving field of epigenetics and its implications in cardiovascular precision medicine.

摘要

心血管疾病(CVDs)仍然是全球死亡的主要原因,也给发病率、生活质量和社会成本带来了重大负担。考虑到 CVD 预防药物在不到一半的患者中改善血管结局(与安慰剂相比,通常相对风险降低幅度在 12%至 20%之间),精准医学提供了一种有吸引力的方法,可以将 CVD 药物的靶向作用细化为人群中的有反应个体,从而更明智和有效地分配资源。基础科学和转化医学的进步提供的新工具可以帮助实现这一目标。这种方法可以超越从业者的“目测”评估或源于体检和标准实验室评估的古老标志物。遗传学的进步已经确定了在许多疾病中起作用的新途径和靶点,为“精准医学”铺平了道路。然而,遗传基因组仅决定个体风险状况的一部分。事实上,标准基因组方法并未考虑到通过“表观基因组”修饰来调节基因表达的世界。表观遗传修饰定义为“基因组的可遗传变化,不涉及 DNA 序列的改变”,已成为 CVD 中生物调节的一个新层面,并可以推进个体化风险评估以及设计和部署量身定制的治疗方法。因此,本综述旨在使心血管界了解表观遗传学这一快速发展和不断演变的领域及其在心血管精准医学中的意义。

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