Peer-reviewedCC BY 4.0International Journal of Molecular Sciences
Targeted DNA Sequencing Reveals Distinct Rare-Variant Profiles in Pulmonary Hypertension Associated with Chronic Lung Diseases
13 affiliations
- 1Department of Pulmonary Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, 08036 Barcelona, Spain
- 2Biomedical Research Networking Centre in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
- 3Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona and Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomediques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain
- 4Bioinformatics Platform, Biomedical Research Networking Centre in Hepatic and Digestive Disease (CIBEREHD), 28029 Madrid, Spain
- 5Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
- 6ERN-LUNG (European Reference Network on Rare Respiratory Diseases), Villarroel 170, 08036 Barcelona, Spain
- 7Translational Research Group on Cardiovascular Respiratory Diseases (CAREs), Dr. Josep Trueta University Hospital de Girona, Avinguda de França, 17007 Girona, Spain
- 8Girona Biomedical Research Institute (IDIBGI-CERCA), Santa Caterina Hospital de Salt, 17190 Salt, Spain
- 9Department of Pulmonary Medicine, Hospital del Mar Research Institute, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
- 10Department of Pulmonary Medicine, Hospital Vall d’Hebron, 08035 Barcelona, Spain
- 11Department of Pulmonary Medicine, Hospital Universitari de Bellvitge, IDIBELL, University of Barcelona, Hospitalet de Llobregat, 08907 Barcelona, Spain
- 12Department of Pulmonary Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA). Universitat Autònoma de Barcelona, 08208 Sabadell, Spain
- 13Department of Experimental Pathology, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain
Abstract
The mechanisms underlying the development and severity of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) remain poorly understood. To investigate the contribution of genetic factors, we performed targeted sequencing of PH-related genes in 63 patients with COPD, 51 with ILD, and 38 with idiopathic pulmonary arterial hypertension (IPAH), stratifying COPD and ILD patients according to PH severity, assessed by right heart catheterisation. Patients with ILD-associated PH harboured fewer genetic variants than those without PH, whereas an opposite trend was observed in COPD-associated PH. Variants of uncertain significance (VUS) in PAH-associated genes (BMPR2, BMPR1B) were identified in two out of 28 patients with severe COPD-PH and in one with nonsevere ILD-PH (SMAD9). VUS in extracellular matrix-related genes (THBS1, LOXL2) were also identified in four patients with severe COPD-PH, and in inflammatory-related genes (TNFAIP6) in two patients with ILD-PH. Pathogenic/likely pathogenic variants in PAH-associated genes were exclusive to IPAH. We conclude that there is limited genetic overlap between COPD-PH and ILD-PH, with a stronger genetic contribution to PH in COPD, particularly in its severe form, where a subset of patients carries VUS in PAH-associated genes or genes involved in vascular remodelling.
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BibTeX
@article{bosacoma2026targeted,
title = {{Targeted DNA Sequencing Reveals Distinct Rare-Variant Profiles in Pulmonary Hypertension Associated with Chronic Lung Diseases}},
author = {Adelaida Bosacoma and Agustín R. Garcia and Irene Madrigal and Juan-José Lozano and Julia Sidorova and Daniel Aguilar and Isabel Blanco and Ylenia Roger and Olga Tura-Ceide and Anna Sardiné-Rama and Clara Martín-Ontiyuelo and Diego A. Rodríguez-Chiaradía and Manuel López-Meseguer and Fernanda Hernandez-Gonzalez and Jesús Ribas and Xavier Pomares and Salud Santos and María Molina-Molina and Rita Fernández-Hernández and Victor I. Peinado and Joan A. Barberà},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208992},
url = {https://www.mdpi.com/1422-0067/27/20/8992},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeted DNA Sequencing Reveals Distinct Rare-Variant Profiles in Pulmonary Hypertension Associated with Chronic Lung Diseases
AU - Adelaida Bosacoma
AU - Agustín R. Garcia
AU - Irene Madrigal
AU - Juan-José Lozano
AU - Julia Sidorova
AU - Daniel Aguilar
AU - Isabel Blanco
AU - Ylenia Roger
AU - Olga Tura-Ceide
AU - Anna Sardiné-Rama
AU - Clara Martín-Ontiyuelo
AU - Diego A. Rodríguez-Chiaradía
AU - Manuel López-Meseguer
AU - Fernanda Hernandez-Gonzalez
AU - Jesús Ribas
AU - Xavier Pomares
AU - Salud Santos
AU - María Molina-Molina
AU - Rita Fernández-Hernández
AU - Victor I. Peinado
AU - Joan A. Barberà
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208992
UR - https://www.mdpi.com/1422-0067/27/20/8992
AB - The mechanisms underlying the development and severity of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) remain poorly understood. To investigate the contribution of genetic factors, we performed targeted sequencing of PH-related genes in 63 patients with COPD, 51 with ILD, and 38 with idiopathic pulmonary arterial hypertension (IPAH), stratifying COPD and ILD patients according to PH severity, assessed by right heart catheterisation. Patients with ILD-associated PH harboured fewer genetic variants than those without PH, whereas an opposite trend was observed in COPD-associated PH. Variants of uncertain significance (VUS) in PAH-associated genes (BMPR2, BMPR1B) were identified in two out of 28 patients with severe COPD-PH and in one with nonsevere ILD-PH (SMAD9). VUS in extracellular matrix-related genes (THBS1, LOXL2) were also identified in four patients with severe COPD-PH, and in inflammatory-related genes (TNFAIP6) in two patients with ILD-PH. Pathogenic/likely pathogenic variants in PAH-associated genes were exclusive to IPAH. We conclude that there is limited genetic overlap between COPD-PH and ILD-PH, with a stronger genetic contribution to PH in COPD, particularly in its severe form, where a subset of patients carries VUS in PAH-associated genes or genes involved in vascular remodelling.
SN - 1422-0067
ER -