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非洲遗传性心肌病的遗传学

Genetics of inherited cardiomyopathies in Africa.

作者信息

Shaboodien Gasnat, Spracklen Timothy F, Kamuli Stephen, Ndibangwi Polycarp, Van Niekerk Carla, Ntusi Ntobeko A B

机构信息

Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

出版信息

Cardiovasc Diagn Ther. 2020 Apr;10(2):262-278. doi: 10.21037/cdt.2019.10.03.

Abstract

In sub-Saharan Africa (SSA), the burden of noncommunicable diseases (NCDs) is rising disproportionately in comparison to the rest of the world, affecting urban, semi-urban and rural dwellers alike. NCDs are predicted to surpass infections like human immunodeficiency virus, tuberculosis and malaria as the leading cause of mortality in SSA over the next decade. Heart failure (HF) is the dominant form of cardiovascular disease (CVD), and a leading cause of NCD in SSA. The main causes of HF in SSA are hypertension, cardiomyopathies, rheumatic heart disease, pericardial disease, and to a lesser extent, coronary heart disease. Of these, the cardiomyopathies deserve greater attention because of the relatively poor understanding of mechanisms of disease, poor outcomes and the disproportionate impact they have on young, economically active individuals. Morphofunctionally, cardiomyopathies are classified as dilated, hypertrophic, restrictive and arrhythmogenic; regardless of classification, at least half of these are inherited forms of CVD. In this review, we summarise all studies that have investigated the incidence of cardiomyopathy across Africa, with a focus on the inherited cardiomyopathies. We also review data on the molecular genetic underpinnings of cardiomyopathy in Africa, where there is a striking lack of studies reporting on the genetics of cardiomyopathy. We highlight the impact that genetic testing, through candidate gene screening, association studies and next generation sequencing technologies such as whole exome sequencing and targeted resequencing has had on the understanding of cardiomyopathy in Africa. Finally, we emphasise the need for future studies to fill large gaps in our knowledge in relation to the genetics of inherited cardiomyopathies in Africa.

摘要

在撒哈拉以南非洲地区(SSA),与世界其他地区相比,非传染性疾病(NCDs)的负担正以不成比例的速度上升,影响着城市、半城市和农村居民。预计在未来十年,非传染性疾病将超过人类免疫缺陷病毒、结核病和疟疾等感染性疾病,成为撒哈拉以南非洲地区主要的死亡原因。心力衰竭(HF)是心血管疾病(CVD)的主要形式,也是撒哈拉以南非洲地区非传染性疾病的主要原因。撒哈拉以南非洲地区心力衰竭的主要原因是高血压、心肌病、风湿性心脏病、心包疾病,以及程度较轻的冠心病。其中,心肌病值得更多关注,因为对其疾病机制的了解相对较少,治疗效果不佳,且对年轻、有经济活动能力的个体影响过大。从形态功能上看,心肌病分为扩张型、肥厚型、限制型和致心律失常型;无论分类如何,其中至少一半是遗传性心血管疾病。在这篇综述中,我们总结了所有在非洲开展的有关心肌病发病率的研究,重点关注遗传性心肌病。我们还回顾了非洲心肌病分子遗传学基础的数据,而目前关于心肌病遗传学的研究报告非常匮乏。我们强调了通过候选基因筛查、关联研究以及全外显子测序和靶向重测序等新一代测序技术进行基因检测,对理解非洲心肌病所产生的影响。最后,我们强调未来的研究需要填补我们在非洲遗传性心肌病遗传学知识方面的巨大空白。

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