Prognostic role of MUC5B rs35705950 genotype in patients with idiopathic pulmonary fibrosis (IPF) on antifibrotic treatment

Abstract

Background: 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. 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.

Methods: 88 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.

Results: Out 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.

Conclusions: In 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.

Keywords: Genetics; Idiopathic pulmonary fibrosis; Interstitial lung diseases; MUC5B; Polymorphisms.

Fig. 1

Progression-free survival of TT/TG and GG genotype patients. The red line represents the progression-free survival in the TT/TG group and the green line represents the progression-free survival in the GG group. Kaplan Meier analysis was used with a log-rank test (HR 1.41, 95% CI 0.81–2.44; p = 0.21)

Fig. 2

Survival analysis of TT/TG and GG genotype patients. The red line represents the survival in the TT/TG group and the green line represents the survival in the GG group. Kaplan Meier analysis was used with a log-rank test (HR 2.59, 95% CI 1.24–5.40; p = 0.0082)

Fig. 3

Combined survival and transplantation analysis of TT/TG and GG genotype patients. The red line represents the analysis in the TT/TG group and the green line represents the analysis in the GG group. Kaplan Meier analysis was used with a log-rank test (HR 2.73, 95% CI 1.34–5.54; p = 0.0038)