Genetics and genomics of pulmonary arterial hypertension.
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
05
10
2018
accepted:
09
10
2018
pubmed:
14
12
2018
medline:
2
10
2020
entrez:
15
12
2018
Statut:
epublish
Résumé
Since 2000 there have been major advances in our understanding of the genetic and genomics of pulmonary arterial hypertension (PAH), although there remains much to discover. Based on existing knowledge, around 25-30% of patients diagnosed with idiopathic PAH have an underlying Mendelian genetic cause for their condition and should be classified as heritable PAH (HPAH). Here, we summarise the known genetic and genomic drivers of PAH, the insights these provide into pathobiology, and the opportunities afforded for development of novel therapeutic approaches. In addition, factors determining the incomplete penetrance observed in HPAH are discussed. The currently available approaches to genetic testing and counselling, and the impact of a genetic diagnosis on clinical management of the patient with PAH, are presented. Advances in DNA sequencing technology are rapidly expanding our ability to undertake genomic studies at scale in large cohorts. In the future, such studies will provide a more complete picture of the genetic contribution to PAH and, potentially, a molecular classification of this disease.
Identifiants
pubmed: 30545973
pii: 13993003.01899-2018
doi: 10.1183/13993003.01899-2018
pmc: PMC6351337
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
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/K020919/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R24 HL105333
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140019
Pays : United States
Organisme : British Heart Foundation
ID : SP/12/12/29836
Pays : United Kingdom
Informations de copyright
Copyright ©ERS 2019.
Déclaration de conflit d'intérêts
Conflict of interest: N.W. Morrell reports grants and personal fees from Morphogen-IX, outside the submitted work. Conflict of interest: M.A. Aldred reports grants from the NIH, during the conduct of the study. Conflict of interest: W.K. Chung has nothing to disclose. Conflict of interest: C.G. Elliott reports personal fees for steering committee work from Bayer and Bellerophon, grants and personal fees for registry and data safety monitoring from Actelion, and was a consultant for end-point adjudication for Lung LLC, with fees paid to his employer (Intermountain Healthcare), outside the submitted work. Conflict of interest: W.C. Nichols has nothing to disclose. Conflict of interest: F. Soubrier has nothing to disclose. Conflict of interest: R.C. Trembath has nothing to disclose. Conflict of interest: J.E. Loyd has nothing to disclose.
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