Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 May;133(5):471-9.
doi: 10.1007/s00439-014-1419-3. Epub 2014 Jan 21.

The genetic basis of pulmonary arterial hypertension

Lijiang Ma  1 , Wendy K Chung
Affiliations
Review

The genetic basis of pulmonary arterial hypertension

Lijiang Ma et al. Hum Genet. 2014 May.

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive elevation of pulmonary artery pressure, pulmonary vascular resistance, right ventricular failure, and a high mortality rate. The etiology of PAH is heterogeneous and incompletely understood. Based on clinical classification, WHO Group 1 PAH includes sporadic disease (idiopathic PAH), inherited PAH (heritable PAH), and association with certain medical conditions (associated PAH). Genes play an important role in idiopathic and heritable PAH. Mutations in bone morphogenetic protein receptor 2 (BMPR2), a member of the transforming growth factor β (TGFβ) superfamily of receptors, have been identified in 70 % of cases of familial PAH, as well as in 10-40 % of cases of idiopathic PAH. Mutations in ALK-1, ENG, SMAD4 and SMAD8, other TGFβ family members, are additional rare causes of PAH. CAV1 regulates SMAD2/3 phosphorylation, and mutations in CAV1 are a rare cause of PAH. KCNK3 is a member of the two-pore domain potassium channels expressed in pulmonary artery smooth muscle cells, and mutations in KCNK3 are a rare cause of both familial and IPAH. The genetics of PAH are complex due to incomplete penetrance and genetic heterogeneity. In addition to rare mutations as a monogenic cause of HPAH, common variants in cerebellin 2 (CBLN2) increase the risk of PAH by approximately twofold. PAH in children is much more heterogeneous than in adults and can be associated with several genetic syndromes, specifically syndromes with congenital heart disease, vascular disease, and hepatic disease. Clinical genetic testing is available for PAH and should be considered in families to allow for more definitive risk stratification and allow for reproductive planning.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Am J Respir Crit Care Med. 2006 May 1;173(9):1023-30 - PubMed
    1. Chest. 2002 Mar;121(3 Suppl):46S-50S - PubMed
    1. J Genet Couns. 2008 Oct;17(5):452-8 - PubMed
    1. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):1055-9 - PubMed
    1. J Biol Chem. 2001 Oct 12;276(41):38121-38 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources