Abstract

Introduction

The minor T-allele of the MUC5B promoter polymorphism rs35705950 is strongly associated with idiopathic pulmonary fibrosis (IPF). Conflicting results have been shown on the effect of the MUC5B risk allele on survival in IPF. We therefore investigated if MUC5B rs35705950 associates with survival in a real world setting in the European IPF population.

Methods

In this retrospective study, 1751 patients with IPF from 8 centers in 6 European countries were included. MUC5B rs35705950 genotype, demographics, clinical characteristics at diagnosis and survival data were collected. 

Results

The number of patients in the GG, GT and TT genotype cohorts were 715 (41%), 908 (52%) and 128 (7%) respectively. Survival analysis showed a significantly better survival for both heterozygous (GT) and homozygous (TT) MUC5B minor allele carriers compared to non-carriers (GG), with a median survival of 49, 45, and 31 months respectively (p= 6·10^-10). The observed association was independent of age, sex, lung function, HRCT pattern, smoking status and treatment with antifibrotic drugs. The percentage of MUC5B minor allele carriers increased significantly with age at diagnosis from 44% in patients younger than 56 years old to 63% in patients over 65 years old. In IPF patients diagnosed at an age younger than 56 years old, the MUC5B genotype no longer associated with survival.

Conclusion

MUC5B minor allele carriage associates with better survival in the European IPF population aged over 56 in a real-world setting. This study identifies a MUC5B associated endotype, particularly in the aged patient with IPF, which is characterised by milder disease behaviour.