Abstract
BackgroundA common variant located in the promoter region of MUC5B (rs35705950) is the strongest risk factor for sporadic and familiar IPF, as well as a predictor of outcome. However, there are no data on the effect of MUC5B rs35705950 genotype on the prognosis of IPF patients on antifibrotic treatment. The aim of this study is to determine, in a phenotypically well-characterized population of patients with IPF treated with antifibrotics, the impact of MUC5B rs35705950 genotype on disease progression and survival.Methods88 IPF patients on antifibrotic treatment were followed-up from 2014 until transplantation, death or end of follow-up (December 2019). Disease progression was defined as a forced vital capacity (FVC) loss ≥ 5% per year. All patients were genotyped for MUC5B rs35705950 by PCR amplification and Sanger sequencing.ResultsOut of 88 patients, 61 (69%) carried the mutant T allele (TT or TG) and 27 (31%) did not (GG). Carriage of the MUC5B rs35705950 T allele was not associated with a faster decline in FVC. Conversely, at the end of the follow-up, overall survival in carriers of the TT/TG genotype was longer compared to that of the GG genotype carriers. FVC (L) at baseline and time to respiratory failure at rest were independent predictors of worse prognosis.ConclusionsIn IPF patients on antifibrotic treatment, carriage of the MUC5B rs35705950 T allele is associated with longer survival, highlighting the usefulness of MUC5B genetic data in clinical decision making.
Highlights
A common variant located in the promoter region of MUC5B is the strongest risk factor for sporadic and familiar Idiopathic pulmonary fibrosis (IPF), as well as a predictor of outcome
The precise mechanisms through which MUC5B dysregulation contributes to IPF development are currently unknown, MUC5B overexpression may cause mucociliary dysfunction, retention of particles and disruption of the normal reparative mechanisms in the distal lung, leading to chronic fibroproliferation and regenerative process that results in honeycomb cyst formation [10,11,12,13,14]
This study shows for the first time that in IPF patients on antifibrotic treatment, survival may be affected by carriage of MUC5B rs35705950 T allele, whether in homozygous or heterozygous form
Summary
A common variant located in the promoter region of MUC5B (rs35705950) is the strongest risk factor for sporadic and familiar IPF, as well as a predictor of outcome. The aim of this study is to determine, in a phenotypically well-characterized population of patients with IPF treated with antifibrotics, the impact of MUC5B rs35705950 genotype on disease progression and survival. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease of unknown origin, characterized by relentless respiratory failure leading to. In 2011, Seibold and colleagues, using a genome-wide linkage analysis, demonstrated that the minor allele (T) of a single nucleotide polymorphism (SNP) located 3 kb Biondini et al Respir Res (2021) 22:98 upstream of the MUC5B gene transcription start site on 11p15 (rs35705950) was present in 38% of subjects with sporadic IPF and in 34% of subjects with familial interstitial pneumonia [3]. The precise mechanisms through which MUC5B dysregulation contributes to IPF development are currently unknown, MUC5B overexpression may cause mucociliary dysfunction, retention of particles and disruption of the normal reparative mechanisms in the distal lung, leading to chronic fibroproliferation and regenerative process that results in honeycomb cyst formation [10,11,12,13,14].
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