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The genetic contribution to idiopathic pulmonary fibrosis (IPF) has become increasingly evident, enabling its translation into clinical practice. MUC5B rs35705950 has emerged as a promising prognostic biomarker. The gender-age-physiology (GAP)-model is regularly used for IPF survival prediction. In this retrospective real-world study, GAP-stages were stratified by MUC5B T-allele carriage. European patients with IPF were included in a discovery (n = 663), and replication (n = 738) cohort. The GAP+MUC5B-model was significantly more accurate compared to the GAP-model (all cohorts p < 0.001), with a modest improvement in discrimination (ΔC = 0.023; C = 0.685, 95%CI 0.665-0.704). Within each GAP-stage, T-allele carriers had significantly better median transplant-free survival outcomes than non-carriers (p < 0.001): In the combined cohort (n = 1401) survival for GAP-stage I T carriers was 70 months (m) vs 48m for T non-carriers; stage II T vs non-T: 41 vs 31m; stage III T vs non-T: 23 vs 12m. Addition of MUC5B rs35705950 T-carriership enhances GAP-based prognostication and aids clinical decision-making.
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http://dx.doi.org/10.1007/s00408-025-00837-z | DOI Listing |
Respirology
August 2025
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background And Objective: Genetic polymorphisms have been associated with susceptibility to interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). We have now examined the relation between single nucleotide polymorphisms (SNPs) and clinical course, including acute exacerbation (AE), in addition to disease susceptibility for IPF and unclassifiable idiopathic interstitial pneumonias (IIPs).
Methods: DNA samples were collected from 223 IPF patients and 160 unclassifiable IIP patients included in a prospective, multicentre observational study in Japan.
RMD Open
August 2025
Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain
Objective: The common gain-of-function variant rs35705950, located in the promoter of gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.
Methods: Samples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays.
Lung
July 2025
ILD Center of Excellence, Member of European Reference Network-Lung, St Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands.
The genetic contribution to idiopathic pulmonary fibrosis (IPF) has become increasingly evident, enabling its translation into clinical practice. MUC5B rs35705950 has emerged as a promising prognostic biomarker. The gender-age-physiology (GAP)-model is regularly used for IPF survival prediction.
View Article and Find Full Text PDFCureus
June 2025
Department of Pulmonology, Hassan II University Hospital Center, Fez, MAR.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology. It has been demonstrated in European, American, and Asian populations that genetic factors, particularly the MUC5B rs35705950 SNP, represent a significant risk factor for the development of this disease. To date, no studies have been performed within African populations, thereby necessitating the execution of the present investigation.
View Article and Find Full Text PDFFront Genet
June 2025
Department of Pulmonology and Critical Care, Hotel Dieu de France Hospital, Beirut, Lebanon.
Background And Objective: Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease that causes irreversible alterations in the architecture of the lung parenchyma, leading to impaired ventilation. Both environmental factors and genetic predisposition play significant roles in the development of IPF. A single nucleotide polymorphism (SNP) (rs35705950) within the promoter of the mucin 5B gene ( has been reported to be associated with the disease; however, no data is available from Lebanon or the Middle East.
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