The features of rare pathogenic BMPR2 variants in pulmonary arterial hypertension: Comparison between patients and reference population.


Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
01 Nov 2020
Historique:
received: 24 10 2019
revised: 02 05 2020
accepted: 29 06 2020
pubmed: 8 7 2020
medline: 15 5 2021
entrez: 8 7 2020
Statut: ppublish

Résumé

Mutations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2) are the most common genetic risk factors underlying pulmonary arterial hypertension (PAH). However, the features of PAH-related BMPR2 rare variants remain unclear. We propose that the discrepancy of BMPR2 rare variants landscape between patients with PAH and reference population would be important to address the genetic background of PAH-related variants. We genotyped BMPR2 rare variants in 670 Chinese patients with pulmonary arterial hypertension. The BMPR2 rare variants were screened in 10,508 reference people from two exome databases. The prevalence of rare BMPR2 variants in patients with PAH was significantly higher compared to the reference population (21.5%, 144/670 vs 0.87%, 91/10508, p = 1.3 × 10 BMPR2 variants located in extracellular ligand-binding domain or altered the amino acid electric status are more pathogenic.

Sections du résumé

BACKGROUND BACKGROUND
Mutations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2) are the most common genetic risk factors underlying pulmonary arterial hypertension (PAH). However, the features of PAH-related BMPR2 rare variants remain unclear. We propose that the discrepancy of BMPR2 rare variants landscape between patients with PAH and reference population would be important to address the genetic background of PAH-related variants.
METHODS METHODS
We genotyped BMPR2 rare variants in 670 Chinese patients with pulmonary arterial hypertension. The BMPR2 rare variants were screened in 10,508 reference people from two exome databases.
RESULTS RESULTS
The prevalence of rare BMPR2 variants in patients with PAH was significantly higher compared to the reference population (21.5%, 144/670 vs 0.87%, 91/10508, p = 1.3 × 10
CONCLUSIONS CONCLUSIONS
BMPR2 variants located in extracellular ligand-binding domain or altered the amino acid electric status are more pathogenic.

Identifiants

pubmed: 32634488
pii: S0167-5273(20)33446-X
doi: 10.1016/j.ijcard.2020.06.068
pii:
doi:

Substances chimiques

BMPR2 protein, human EC 2.7.11.30
Bone Morphogenetic Protein Receptors, Type II EC 2.7.11.30

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

138-143

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Zi-Chao Lyu (ZC)

Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Lan Wang (L)

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Jian-Hui Lin (JH)

Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.

Su-Qi Li (SQ)

Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Dan-Chen Wu (DC)

Department of Medicine, Queen's University, Kingston, Ontario, Canada.

Tian-Yu Lian (TY)

Laboratory of Clinical Genetics, Medical Science Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Shao-Fei Liu (SF)

Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Jue Ye (J)

Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Xin Jiang (X)

Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Xiao-Jian Wang (XJ)

Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: wang_xiaojian@vip.163.com.

Zhi-Cheng Jing (ZC)

Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: jingzhicheng@vip.163.com.

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Classifications MeSH