The Complex and Diverse Genetic Architecture of Dilated Cardiomyopathy.
The Complex and Diverse Genetic Architecture of Dilated Cardiomyopathy.
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DOI：
10.1161/circresaha.121.318157
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发表时间：
2021-05-14
影响因子：
20.1
通讯作者：
Kinnamon DD
中科院分区：
文献类型：
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作者：
Hershberger RE;Cowan J;Jordan E;Kinnamon DD
我们对扩张型心肌病（DCM）遗传结构的多样性和复杂性的认识继续迅速发展。DCM的遗传学基础在于显著的基因座和等位基因异质性。虽然DCM在某些家族中表现出孟德尔单基因结构，但我们研究和其他研究的初步数据表明，至少20-30%的DCM可能具有寡基因基础，这意味着来自不同非连锁基因座的多种罕见变体决定了DCM表型。低频率和常见的遗传变异也可能导致DCM的复杂性，但在罕见的变异背景下也没有进行过研究。其他类型的遗传变异也可能与扩张型心肌病相关，沿着基因与环境的相互作用，目前已确定与酒精和化疗相关的扩张型心肌病。总的来说，这表明DCM的遗传结构比以前理解的范围更广，更复杂。所有这些都提升了DCM遗传学研究的影响，因为更深入地了解DCM的原因可以导致干预措施来减轻甚至预防它，从而避免人类心力衰竭的病态和致命的祸害。
Our insight into the diverse and complex nature of dilated cardiomyopathy (DCM) genetic architecture continues to evolve rapidly. The foundations of DCM genetics rest on marked locus and allelic heterogeneity. While DCM exhibits a Mendelian, monogenic architecture in some families, preliminary data from our studies and others suggests that at least 20–30% of DCM may have an oligogenic basis, meaning that multiple rare variants from different, unlinked loci, determine the DCM phenotype. It is also likely that low-frequency and common genetic variation contribute to DCM complexity, but neither has been examined within a rare variant context. Other types of genetic variation are also likely relevant for DCM, along with gene-by-environment interaction, now established for alcohol- and chemotherapy-related DCM. Collectively, this suggests that the genetic architecture of DCM is broader in scope and more complex than previously understood. All of this elevates the impact of DCM genetics research, as greater insight into the causes of DCM can lead to interventions to mitigate or even prevent it, and thus avoid the morbid and mortal scourge of human heart failure.