The genetics of pulmonary arterial hypertension in the post-BMPR2 era.
The genetics of pulmonary arterial hypertension in the post-BMPR2 era.
复制标题
后 BMPR2 时代的肺动脉高压遗传学。
DOI：
10.4103/2045-8932.87293
复制
发表时间：
2011-07
影响因子：
2.6
通讯作者：
Austin ED
中科院分区：
文献类型：
--
作者：
Fessel JP;Loyd JE;Austin ED
肺动脉高压（PAH）是一种进展迅速的致死性疾病，其发病机制的遗传和相关病理生理信息不断增加。已知的最常见的单一罪魁祸首基因是BMPR2，并且存在几种形式的疾病动物模型。关于疾病表达、外显率和严重程度的修饰因子有丰富的遗传数据。尽管在过去十年中数据迅速积累，但PAH分子发病机制的完整图景导致新疗法缺乏。在这篇综述中，我们试图从遗传学的角度总结目前对多环芳烃的认识。讨论了最近的多环芳烃人口统计数据。后bmpr2时代的可遗传性多环芳烃作为动物模型和人类系谱中多环芳烃遗传最可靠的模型进行了详细的研究。本文综述了PAH发病机制的重要下游分子通路和疾病表达修饰因子。当前和新兴的治疗方法是根据遗传数据进行检查的。讨论了后bmpr2时代基因检测在PAH中的作用。最后，讨论了未来研究的方向，这些方向将理想地实现新的治疗或预防策略的承诺。
Pulmonary arterial hypertension (PAH) is a rapidly progressive and fatal disease for which there is an ever-expanding body of genetic and related pathophysiological information on disease pathogenesis. The most common single culprit gene known is BMPR2, and animal models of the disease in several forms exist. There is a wealth of genetic data regarding modifiers of disease expression, penetrance, and severity. Despite the rapid accumulation of data in the last decade, a complete picture of the molecular pathogenesis of PAH leading to novel therapies is lacking. In this review, we attempt to summarize the current understanding of PAH from the genetic perspective. The most recent PAH demographics are discussed. Heritable PAH in the post-BMPR2 era is examined in detail as the most robust model of PAH genetics in both animal models and human pedigrees. Important downstream molecular pathways and modifiers of disease expression are reviewed in light of what is known about PAH pathogenesis. Current and emerging therapies are examined in light of genetic data. The role of genetic testing in PAH in the post-BMPR2 era is discussed. Finally, directions for future investigations that ideally will fulfill the promise of novel therapeutic or preventive strategies are discussed.