Genetics and genomics of pulmonary arterial hypertension
Genetics and genomics of pulmonary arterial hypertension
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DOI：
10.1183/13993003.01899-2018
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发表时间：
2019-01-01
影响因子：
24.3
通讯作者：
Loyd, James E.
中科院分区：
文献类型：
--
作者：
Morrell, Nicholas W.;Aldred, Micheala A.;Loyd, James E.
自2000年以来，我们对肺动脉高压（PAH）的遗传和基因组学的理解取得了重大进展，尽管仍有许多有待发现。根据现有的知识，大约25-30%的特发性多环芳烃患者的病情有潜在的孟德尔遗传原因，应归类为遗传性多环芳烃（HPAH）。在这里，我们总结了已知的多环芳烃遗传和基因组驱动因素，这些见解为病理生物学提供了见解，并为开发新的治疗方法提供了机会。此外，还讨论了影响HPAH不完全外显率的因素。目前可用的方法，基因检测和咨询，遗传诊断对临床管理的病人多环芳烃的影响，提出。DNA测序技术的进步正在迅速扩大我们在大型队列中进行大规模基因组研究的能力。在未来，这样的研究将提供一个更完整的图谱，遗传贡献多环芳烃和潜在的分子分类这种疾病。
Since 2000 there have been major advances in our understanding of the genetic and genomics of pulmonary arterial hypertension (PAH), although there remains much to discover. Based on existing knowledge, around 25-30% of patients diagnosed with idiopathic PAH have an underlying Mendelian genetic cause for their condition and should be classified as heritable PAH (HPAH). Here, we summarise the known genetic and genomic drivers of PAH, the insights these provide into pathobiology, and the opportunities afforded for development of novel therapeutic approaches. In addition, factors determining the incomplete penetrance observed in HPAH are discussed. The currently available approaches to genetic testing and counselling, and the impact of a genetic diagnosis on clinical management of the patient with PAH, are presented. Advances in DNA sequencing technology are rapidly expanding our ability to undertake genomic studies at scale in large cohorts. In the future, such studies will provide a more complete picture of the genetic contribution to PAH and, potentially, a molecular classification of this disease.