Association between MUC5B rs35705950 genotype and response to antifibrotic treatment in patients with Idiopathic Pulmonary Fibrosis (IPF)

Abstract

Background: MUC5B polymorphism rs35705950 (T) is the strongest genetic risk factor for familiar and sporadic IPF as well as a predictor of outcome. No study has yet investigated the impact of MUC5B genotype on response to treatment and disease behavior in IPF patients on antifibrotic treatment. Aim: To determine whether MUC5B genotype (GGvs.TT/TG) affects functional decline and survival of IPF patients on antifibrotic therapy (pirfenidone or nintedanib). Methods: 88 IPF patients on antifibrotic treatment were followed from treatment initiation until transplantation or death. Time to progression was defined as the time (months) from treatment initiation to an absolute decline in forced vital capacity (FVC)%pred≥5%. All patients were genotyped for MUC5B rs35705950 by PCR amplification and Sanger sequencing. Results: 61/88 patients (69%) carried the minor T allele (TT/TG) while 27/88 (31%) did not (GG). Carriers of the T allele displayed similar FVC loss in the 1-year of treatment and time to progression (19vs.20 months, HR 0.86, 95%CI0.49–1.50;p= 0.59) compared to GG carriers. However, at the end of the follow-up, overall survival was significantly longer in carriers of the mutant T allele (TT/GT) compared to that of GG (56vs.41 months, HR 0.40, 95%CI 0.18–0.91;p= 0.006). FVC(ml) at baseline and time to occurrence of respiratory failure at rest were additional independent predictors of mortality. Conclusions: Carriage of MUC5B rs35705950 T allele is associated with longer survival in IPF patients on antifibrotic therapy and may potentially be useful as predictor of outcome. More data are needed to unravel the mechanisms underlying this association.