title: BMPR2 mutation is a potential predisposing genetic risk factor for congenital heart disease associated pulmonary vascular disease.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, China.
authors.forename: Da-Xin
authors.initials: DX
authors.lastname: Zhou
authors.affiliation: Pediatric Cardiology Unit, Department of the Child and Adolescent, Children's University Hospital, Geneva, Switzerland.
authors.forename: Maurice
authors.initials: M
authors.lastname: Beghetti
authors.affiliation: 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.
authors.forename: Jie-Ming
authors.initials: JM
authors.lastname: Qu
authors.affiliation: 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.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D000293:Adolescent; D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012307:Risk Factors; D014655:Vascular Resistance / Q000235:genetics*; D055815:Young Adult
chemical_list: C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: Bone morphogenetic protein receptor 2; Congenital heart disease; Pulmonary arterial hypertension; Pulmonary vascular disease