Details

Autor(en) / Beteiligte

• Wang, Xiao-Jian
• Lian, Tian-Yu
• Jiang, Xin
• Liu, Shao-Fei
• Li, Su-Qi
• Jiang, Rong
• Wu, Wen-Hui
• Ye, Jue
• Cheng, Chun-Yan
• Du, Yao
• Xu, Xi-Qi
• Wu, Yan
• Peng, Fu-Hua
• Sun, Kai
• Mao, Yi-Min
• Yu, Huan
• Liang, Chen
• Shyy, John Y-J
• Zhang, Shu-Yang
• Zhang, Xue
• Jing, Zhi-Cheng

Titel

Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension

Ist Teil von

• The European respiratory journal, 2019-03, Vol.53 (3), p.1801609

Ort / Verlag

England

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a large number of IPAH cases. We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function. The gene encoding human bone morphogenetic protein 9 ( ) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10 ). This association was authenticated in the independent replication cohort (p=1.0×10 ). Collectively, the rare coding mutations in occurred in 6.7% of cases, ranking this gene second to , comprising a combined significance of 2.7×10 (OR 21.2). Intriguingly, the patients with mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells. We identify as an IPAH culprit gene.