Dong Liu1, Qian-Qian Liu2, Li-Hua Guan3, Xin Jiang4, Da-Xin Zhou3, Maurice Beghetti5, Jie-Ming Qu6, Zhi-Cheng Jing7. 1. Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China; Department of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 2. Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. 3. Department of Cardiology, Zhongshan Hospital, Fudan University, China. 4. State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China. 5. Pediatric Cardiology Unit, Department of the Child and Adolescent, Children's University Hospital, Geneva, Switzerland. 6. Department of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China. Electronic address: jmqu0906@163.com. 7. Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China; State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China. Electronic address: jingzhicheng@vip.163.com.
Abstract
BACKGROUND: Pulmonary arterial hypertension (PAH) frequently arises in patients with congenital heart disease (CHD) and can lead to pulmonary vascular disease (PVD). The present study was initiated to distinguish the predisposing effect of bone morphogenetic protein receptor 2 (BMPR2) in CHD by comparing the different mutation features of BMPR2 between CHD patients with or without PVD. METHODS AND RESULTS: 294 CHD-PVD and 161 CHD without PVD patients were enrolled. PAH was diagnosed by heart catheterization at rest after CHD was first recognized by echocardiography. PVD was defined as a pulmonary vascular resistance (PVR) more than 3 Wood units. BMPR2 gene was screened by direct sequencing. A total of 24 mutations were identified, accounting for 22 of the 294 patients with CHD-PVD (7.5%) and 2 of the 161 CHD patients without PVD (1.2%, P=0.004). Female/male CHD-PVD patient ratio was 1.6:1, while in the BMPR2 mutation carriers female patients were more dominant (4.5:1, P=0.042). A significant higher BMPR2 mutation rate (12.6%) was found in repaired CHD-PVD (P=0.010). BMPR2 mutations in CHD-PVD patients were identified in different clinical phenotypes. Missense mutation of BMPR2 is the dominant mutation type. CONCLUSION: Genetic predisposing factor may be an important component in the process of development of PVD in CHD patients. Female, repaired patients are more likely to be detected with genetic mutations.
BACKGROUND:Pulmonary arterial hypertension (PAH) frequently arises in patients with congenital heart disease (CHD) and can lead to pulmonary vascular disease (PVD). The present study was initiated to distinguish the predisposing effect of bone morphogenetic protein receptor 2 (BMPR2) in CHD by comparing the different mutation features of BMPR2 between CHD patients with or without PVD. METHODS AND RESULTS: 294 CHD-PVD and 161 CHD without PVD patients were enrolled. PAH was diagnosed by heart catheterization at rest after CHD was first recognized by echocardiography. PVD was defined as a pulmonary vascular resistance (PVR) more than 3 Wood units. BMPR2 gene was screened by direct sequencing. A total of 24 mutations were identified, accounting for 22 of the 294 patients with CHD-PVD (7.5%) and 2 of the 161 CHD patients without PVD (1.2%, P=0.004). Female/male CHD-PVDpatient ratio was 1.6:1, while in the BMPR2 mutation carriers female patients were more dominant (4.5:1, P=0.042). A significant higher BMPR2 mutation rate (12.6%) was found in repaired CHD-PVD (P=0.010). BMPR2 mutations in CHD-PVD patients were identified in different clinical phenotypes. Missense mutation of BMPR2 is the dominant mutation type. CONCLUSION: Genetic predisposing factor may be an important component in the process of development of PVD in CHD patients. Female, repaired patients are more likely to be detected with genetic mutations.
Authors: Erika B Rosenzweig; Steven H Abman; Ian Adatia; Maurice Beghetti; Damien Bonnet; Sheila Haworth; D Dunbar Ivy; Rolf M F Berger Journal: Eur Respir J Date: 2019-01-24 Impact factor: 16.671
Authors: Ignacio Hernandez-Gonzalez; Jair Tenorio; Julian Palomino-Doza; Amaya Martinez Meñaca; Rafael Morales Ruiz; Mauro Lago-Docampo; María Valverde Gomez; Javier Gomez Roman; Ana Belén Enguita Valls; Carmen Perez-Olivares; Diana Valverde; Joan Gil Carbonell; Elvira Garrido-Lestache Rodríguez-Monte; Maria Jesus Del Cerro; Pablo Lapunzina; Pilar Escribano-Subias Journal: PLoS One Date: 2020-04-29 Impact factor: 3.240