Genetics variants in familial interstitial pneumonia and progressive fibrosing interstitial lung disease (PF-ILD)

Abstract

<b>Background:</b> Familial interstitial pneumonia (FIP) is defined by two or more members of the same family with interstitial lung disease. Rare variants in genes related to surfactant production, TERT, TERC and short age-adjusted leukocyte telomere length and the polymorphism rs35705950 at MUC5B are the most common genetic alterations related to FIP. <b>Objectives:</b> Investigate the association between genetics polymorphisms and Progressive Fibrosing Interstitial Lung Disease (PF-ILD) in FIP followed at a university hospital. <b>Methods:</b> Data were collected from medical records and blood samples collected for genetic analysis. Real-time PCR genotyping was performed using TaqMan probes for each of the single-nucleotide polymorphisms. The next generation sequencing data were analyzed using the GATK tools and the variants found were classified according to the American College of Medical Genetics and Genomics criteria. PF-ILD was defined as any of following: death in first two years, exacerbation, decline in forced vital capacity (FVC%)≥10% of predicted values or when 2 or 3 of the following findings were found: FVC% decline between 5-9%, worsening of dyspnea and increasing extent of fibrotic changes on tomographic scans. Findings related to PF-ILD were selected by chi-square test and t-test. <b>Results:</b> Forty-one participants were included. Mean age was 67±8 years, 18 were male. Twelve had PF-ILD. Frequency of polymorphisms were:75,6% of MUC5B_rs35705950, 78% of TERT_rs2736100, 19,5% of TOLLIP_rs5743894, 19,5% of TOLLIP_rs11521887, 2,4% of TOLLIP_rs5743890. Only TERT_rs2736100 variant were associated to PF-ILD (p=0,039). <b>Conclusions:</b> TERT_rs2736100 variant is associated to PF-ILF in FIP.