Abstract

Inês Luís (Portugal)^{1 2}; Rita F. Santos (Portugal)^{3 2}; Nuno Osório (Portugal)⁴; Diana Gomes (Portugal)^{1 5}; Andreia Coelho (Portugal)³; Mariana Resende (Portugal)³; David Coelho (Portugal)^{1 5 6}; Janete Santos (Portugal)^{1 5}; Oksana Sokhatska (Portugal)⁷; Marília Beltrão (Portugal)⁷; Natália Melo (Portugal)⁶; Patrícia Mota (Portugal)^{1 5 6}; André Terras (Portugal)⁶; André Carvalho (Portugal)^{1 8}; Susana Guimarães (Portugal)^{1 9}; Conceição Souto Moura (Portugal)^{1 9}; Ana Grangeia (Portugal)^{1 10}; António Morais (Portugal)^{1 5 6}; Hélder Novais Bastos (Portugal)^{1 5 6};

1 - Faculty of Medicine of the University of Porto; 2 - E2S-IPP, School of Health, Polytechnic of Porto, Porto, Portug; 3 - i3S –Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; 4 - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; 5 - RISE-Health, Faculty of Medicine of the University of Porto; 6 - Department of Pulmonology, Unidade Local de Saúde de São João, Alameda Prof. Hernâni Monteiro, Porto, 4200-319, Portugal; 7 - Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal; 8 - Department of Radiology, Unidade Local de Saúde de São João, Porto, Portugal; 9 - Department of Pathology, Unidade Local de Saúde de São João, Porto, Portugal; 10 - Department of Genetics, Unidade Local de Saúde de São João, Porto, Portugal;

Select the theme: Genetics and Immunopathology: Advances in Contemporary Understanding and Prospects for Future Research
Type: Original Papers
Presentation: Poster Presentation

Introduction: Variants in telomere-related genes (TRG), including TERT, TERC, RTEL1, DKC1, and PARN, have been implicated in familial pulmonary fibrosis. Their role in sporadic idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (HP) remains unclear.

Objectives: To assess the frequency of pathogenic or likely pathogenic telomere-related gene variants and their association with clinical characteristics and disease progression in IPF and fibrotic HP.

Materials and Methods: We analyzed 73 patients with fibrotic interstitial lung disease (48 HP, 25 IPF) and 91 controls. Genomic DNA was extracted, and SNP genotyping of eight selected candidate loci was performed using the Axiom™ Human Genotyping SARS-CoV-2 Array (Thermo Fisher Scientific). The selected variants were previously reported as pathogenic or likely pathogenic in ClinVar and the literature. Disease progression was defined according to ATS/ERS criteria.

Results: IPF patients were predominantly male (96.2% vs 49.0%, p<0.001), older (72.5 vs 70.0 years, p=0.01), and less frequently exposed to environmental antigens (46.2% vs 72.5%, p=0.023). A family history of pulmonary fibrosis was reported in 10 of 73 patients (8 HP, 2 IPF). Baseline lung function, progression rates, and overall survival were similar between the IPF and HP cohorts. Pathogenic or likely pathogenic TRG variants were identified in 52% (n=13) of IPF patients, while no variants were detected in HP or controls (p < 0.001). The most frequent findings involved TERT variants, specifically rs776981958 (n=10) and rs199422300 (n=8), which often occurred in combination. Other identified variants included DKC1 (rs1057520719, rs199422245) and RTEL1 (rs116247954).

Conclusions: TRG variants were found in half of IPF patients, but were entirely absent in HP and controls, suggesting a distinct genetic contribution to IPF. These findings support the potential role of genetic screening in fibrotic interstitial lung disease, although interpretation should consider the limited sample size and partial genotyping coverage.