ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2558

Bone Morphogenic Protein Receptor 2 (BMPR2) Gene Mutations Are Associated To The Development Of Isolated Pulmonary Arterial Hypertension (PAH) In Systemic Sclerosis (SSc) Patients

Tatiana Sofia Rodriguez-Reyna1, Jose Luis Hernandez-Oropeza2, Tomas Rene Pulido-Zamudio3, Felipe Massó4, Jessica Gutierrez-Manjarrez1, Alexandra Rueda de Leon-Aguirre1, Julio Sandoval-Zarate3 and Carlos Rodriguez-Osorio5, 1Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico, 2Pulmonary Circulation Clinic, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico, 3Pulmonary Circulation Clinic, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico, 4Immunology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico, 5Intensive Care Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Genetic Biomarkers, Pulmonary Involvement and systemic sclerosis

  • Tweet
  • Email
  • Print
Session Information

Session Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud's II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Isolated pulmonary arterial hypertension (PAH) secondary to Systemic Sclerosis (SSc) is a severe life-threatening complication. Several pathogenic pathways have been implicated in its development. Bone morphogenic protein receptor 2 (BMPR2) is a protein of the TGF-beta receptor superfamily; mutations in this gene seem to be implicated in the proliferation of pulmonary artery smooth muscle cells, a major component of pulmonary arteriolar remodeling in PAH, and they have been associated to the susceptibility to develop idiopathic and familial PAH; exon 5 has higher frequency of mutations according to previous analyses. The aim of this study was to evaluate if BMPR2 gene exon 5 mutations are associated to isolated PAH in Mexican Mestizo SSc patients.

Methods: DNA samples from 38 Mexican Mestizo SSc patients with isolated PAH (mean resting pulmonary artery pressure (PAP) >25 mmHg, pulmonary wedge pressure < 15 mmHg and pulmonary vascular resistance > 3 Wood units by right side catheterization; or systolic PAP >40 mmHg, tricuspid annular plane systolic excursion <20 mmHg and dilatation and hypertrophy of right ventricle by transthoracic echocardiogram; patients were also required to have no or minimal interstitial lung disease by computed tomography) and 38 Mexican Mestizo SSc patients without PAH, matched by SSc subtype, age (+/- 5 years), gender, time of evolution of the disease and SSc-associated autoantibody were analyzed. High resolution melting analysis (HRMA) of exon 5 of the BMPR2 gene was performed in previously amplified DNA (sense primer: 5ˈTCA TGC TAT TCT GCA TTC ATC.3ˈ, antisense primer: 5ˈCAG GTC TAG TAT CAC AGT AGA.3ˈ). Aberrant curves were considered as positive for mutation in the exon 5 of the BMPR2 gene. Severity of the organ involvement was evaluated using the Medsger severity scale. Statistical analysis was performed using SPSS v.19 and Epi-Info 7.0. Chi square was used to compare mutation frequencies between groups; Student’s t test and Wilcoxon rank test were used to compare numeric variables. Values were considered significant when two-tailed p values were <0.05.

Results: Mean age was 50 years, mean time of SSc evolution was 12.25 years, 80% of patients were female, with no differences between PAH and non-PAH patients. Mean PAP was 57 mmHg in PAH-SSc patients and 25 mmHg in non-PAH-SSc patients (p<0.001); BMPR2 gene exon 5 mutations were detected in 7 (18%) of PAH-SSc patients and in 1 (3%) non-PAH-SSc patient (p=0.001, OR: 31, 95% CI 5.1-1263). From the 7 patients with PAH that had a mutation, 6 were female, 6 had limited cutaneous SSc, 6 had severe vascular involvement (digital ulcers and/or gangrene at any time of the evolution of the disease), 1 had anti-Topoisomerase I and 2 had anti-U1-RNP antibody. Prevalence of BMPR2 gene exon 5 mutation in our sample was 11%.

Conclusion: Prevalence of BMPR2 gene exon 5 mutations in PAH-SSc patients is higher than in non-PAH-SSc patients; prevalence of BMPR2 gene exon 5 mutations in this SSc sample is similar to the prevalence reported in some idiopathic PAH studies; our results suggest that BMPR2 gene exon 5 mutations increase the risk to develop PAH in Mexican Mestizo SSc patients.


Disclosure:

T. S. Rodriguez-Reyna,
None;

J. L. Hernandez-Oropeza,
None;

T. R. Pulido-Zamudio,
None;

F. Massó,
None;

J. Gutierrez-Manjarrez,
None;

A. Rueda de Leon-Aguirre,
None;

J. Sandoval-Zarate,
None;

C. Rodriguez-Osorio,
None.

  • Tweet
  • Email
  • Print

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/bone-morphogenic-protein-receptor-2-bmpr2-gene-mutations-are-associated-to-the-development-of-isolated-pulmonary-arterial-hypertension-pah-in-systemic-sclerosis-ssc-patients/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies