open access

Vol 76, No 5 (2018)
Original articles
Published online: 2018-01-19
Submitted: 2017-10-02
Accepted: 2018-01-18
Get Citation

Genetic variants in a Polish population of patients with pulmonary arterial hypertension: sequencing of BMPR2, ALK1, and ENG genes

Barbara Uznańska-Loch, Kamil Wikło, Dominika Kulczycka-Wojdala, Bożena Szymańska, Łukasz Chrzanowski, Karina Wierzbowska-Drabik, Ewa Trzos, Jarosław D. Kasprzak, Małgorzata Kurpesa
DOI: 10.5603/KP.a2018.0034
·
Kardiol Pol 2018;76(5):852-859.

open access

Vol 76, No 5 (2018)
Original articles
Published online: 2018-01-19
Submitted: 2017-10-02
Accepted: 2018-01-18

Abstract

Background:

Pulmonary arterial hypertension (PAH) is a rare disease with a very serious prognosis. It seems that mutations in genes related to transforming growth factor-b signalling pathway are often related to the development of the disease. No study covers this problem in a Polish population.


Aim:

To screen for genetic mutations in a Polish cohort of patients with pulmonary hypertension, especially with idiopathic PAH, treated in a single hospital in Poland.


Methods:

DNA sequencing method was used. Samples from 50 patients with pulmonary hypertension were screened for mutations in type 2 bone morphogenetic protein receptor of the transforming growth factor-b superfamily gene (BMPR2). Samples from 20 patients with idiopathic PAH (11 men, mean age 55 years) were also screened for mutations in activin A receptor-like type 1 gene (ALK1) and endoglin gene (ENG).


Results:

No genetic variations were found for the BMPR2 gene. In all 20 samples from idiopathic pulmonary hypertension patients we found heterozygosity of single nucleotide polymorphism (SNP) rs 372023206 in ALK1 gene. Three samples from these patients showed variations of ENG gene: we found one sample with heterozygosity of SNP rs 200525684, one with heterozygosity of SNP rs 3739817, and one with both.


Conclusions:

We detected benign polymorphisms or genetic variants of unknown importance. It is possible that the Polish population of PAH patients differs from the previously described populations of other countries in terms of the frequency and importance of mutations in BMPR2, ALK1 and ENG genes.

Abstract

Background:

Pulmonary arterial hypertension (PAH) is a rare disease with a very serious prognosis. It seems that mutations in genes related to transforming growth factor-b signalling pathway are often related to the development of the disease. No study covers this problem in a Polish population.


Aim:

To screen for genetic mutations in a Polish cohort of patients with pulmonary hypertension, especially with idiopathic PAH, treated in a single hospital in Poland.


Methods:

DNA sequencing method was used. Samples from 50 patients with pulmonary hypertension were screened for mutations in type 2 bone morphogenetic protein receptor of the transforming growth factor-b superfamily gene (BMPR2). Samples from 20 patients with idiopathic PAH (11 men, mean age 55 years) were also screened for mutations in activin A receptor-like type 1 gene (ALK1) and endoglin gene (ENG).


Results:

No genetic variations were found for the BMPR2 gene. In all 20 samples from idiopathic pulmonary hypertension patients we found heterozygosity of single nucleotide polymorphism (SNP) rs 372023206 in ALK1 gene. Three samples from these patients showed variations of ENG gene: we found one sample with heterozygosity of SNP rs 200525684, one with heterozygosity of SNP rs 3739817, and one with both.


Conclusions:

We detected benign polymorphisms or genetic variants of unknown importance. It is possible that the Polish population of PAH patients differs from the previously described populations of other countries in terms of the frequency and importance of mutations in BMPR2, ALK1 and ENG genes.

Get Citation

Keywords

genetic mutations, pulmonary arterial hypertension, BMPR2 gene, ALK1 gene, ENG gene

About this article
Title

Genetic variants in a Polish population of patients with pulmonary arterial hypertension: sequencing of BMPR2, ALK1, and ENG genes

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 76, No 5 (2018)

Pages

852-859

Published online

2018-01-19

DOI

10.5603/KP.a2018.0034

Bibliographic record

Kardiol Pol 2018;76(5):852-859.

Keywords

genetic mutations
pulmonary arterial hypertension
BMPR2 gene
ALK1 gene
ENG gene

Authors

Barbara Uznańska-Loch
Kamil Wikło
Dominika Kulczycka-Wojdala
Bożena Szymańska
Łukasz Chrzanowski
Karina Wierzbowska-Drabik
Ewa Trzos
Jarosław D. Kasprzak
Małgorzata Kurpesa

References (11)
  1. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016; 37(1): 67–119.
  2. Machado RD, Aldred MA, James V, et al. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat. 2006; 27(2): 121–132.
  3. Soubrier F, Chung WK, Machado R, et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2013; 62(25 Suppl): D13–D21.
  4. Berg JN, Gallione CJ, Stenzel TT, et al. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet. 1997; 61(1): 60–67.
  5. Pousada G, Baloira A, Fontán D, et al. Mutational and clinical analysis of the ENG gene in patients with pulmonary arterial hypertension. BMC Genetics. 2016; 17(1): 72.
  6. Ponikowski P, Voors AA, Anker SD, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37(27): 2129–2200.
  7. Machado RD, Southgate L, Eichstaedt CA, et al. Pulmonary Arterial Hypertension: A Current Perspective on Established and Emerging Molecular Genetic Defects. Hum Mutat. 2015; 36(12): 1113–1127.
  8. Koehler R, Grünig E, Pauciulo MW, et al. Low frequency of BMPR2 mutations in a German cohort of patients with sporadic idiopathic pulmonary arterial hypertension. J Med Genet. 2004; 41(12): e127.
  9. Jachec W, Foremny A, Domal-Kwiatkowska D, et al. Expression of TGF-beta1 and its receptor genes (TbetaR I, TbetaR II, and TbetaR III-betaglycan) in peripheral blood leucocytes in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome. Int J Mol Med. 2008; 21(1): 99–107.
  10. Morrell NW, Yang X, Upton PD, et al. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation. 2001; 104(7): 790–795.
  11. Girerd B, Montani D, Coulet F, et al. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med. 2010; 181(8): 851–861.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., Świętokrzyska 73 street, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl