Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers

Abstract

A single-nucleotide polymorphism (rs35705950) in the mucin 5B (MUC5B) gene promoter is associated with pulmonary fibrosis and interstitial features on chest CT but may also have beneficial effects. In non-Hispanic whites in the COPDGene cohort with interstitial features (n=454), the MUC5B promoter polymorphism was associated with a 61% lower odds of a prospectively reported acute respiratory disease event (P=0.001), a longer time-to-first event (HR=0.57; P=0.006) and 40% fewer events (P=0.016). The MUC5B promoter polymorphism may have a beneficial effect on the risk of acute respiratory disease events in smokers with interstitial CT features.

Trial registration: ClinicalTrials.gov NCT00608764.

Keywords: copd exacerbations; idiopathic pulmonary fibrosis; interstitial fibrosis.

Conflict of interest statement

Competing interests: SYA, RH, RKP and RSJE report no other relevant disclosures. GMH reports consulting for Medna LLC, and Gerson Lehrman Group, and has served on a scientific advisory boards for Genentech and Boehringer-Ingelheim. GRW reports other support from Genentech, GlaxoSmithKline, PulmonX, and Janssen.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Proposed schema for the relationship between the MUC5B promoter polymorphism, interstitial features and ARD events. Note that we hypothesise that those individuals with interstitial features are those with the greatest evidence of increased MUC5B expression and therefore those most likely to have the normalised MUC5B/MUC5AC ratio. ARD, acute respiratory disease.