Htet Myo, Lei Shunyao, Bajpayi Sheetal, Zoitou Asimina, Chamakioti Myrsini, Tampakakis Emmanouil
Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States.
Front Cardiovasc Med. 2023 May 22;10:1116925. doi: 10.3389/fcvm.2023.1116925. eCollection 2023.
Cardiomyopathies remain one of the leading causes of morbidity and mortality worldwide. Environmental risk factors and genetic predisposition account for most cardiomyopathy cases. As with all complex diseases, there are significant challenges in the interpretation of the molecular mechanisms underlying cardiomyopathy-associated genetic variants. Given the technical improvements and reduced costs of DNA sequence technologies, an increasing number of patients are now undergoing genetic testing, resulting in a continuously expanding list of novel mutations. However, many patients carry noncoding genetic variants, and although emerging evidence supports their contribution to cardiac disease, their role in cardiomyopathies remains largely understudied. In this review, we summarize published studies reporting on the association of different types of noncoding variants with various types of cardiomyopathies. We focus on variants within transcriptional enhancers, promoters, intronic sites, and untranslated regions that are likely associated with cardiac disease. Given the broad nature of this topic, we provide an overview of studies that are relatively recent and have sufficient evidence to support a significant degree of causality. We believe that more research with additional validation of noncoding genetic variants will provide further mechanistic insights on the development of cardiac disease, and noncoding variants will be increasingly incorporated in future genetic screening tests.
心肌病仍然是全球发病和死亡的主要原因之一。环境风险因素和遗传易感性是大多数心肌病病例的病因。与所有复杂疾病一样，在解释心肌病相关基因变异的分子机制方面存在重大挑战。鉴于DNA测序技术的技术改进和成本降低，现在越来越多的患者正在接受基因检测，导致新突变的清单不断扩大。然而，许多患者携带非编码基因变异，尽管新出现的证据支持它们对心脏病的影响，但其在心肌病中的作用仍 largely understudied。在本综述中，我们总结了已发表的关于不同类型非编码变异与各种类型心肌病关联的研究。我们关注转录增强子、启动子、内含子位点和非翻译区中可能与心脏病相关的变异。鉴于该主题的广泛性，我们概述了相对较新且有足够证据支持显著因果关系程度的研究。我们相信，对非编码基因变异进行更多的额外验证研究将为心脏病的发展提供进一步的机制见解，并且非编码变异将越来越多地纳入未来的基因筛查测试中。
