Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis

Interstitial Lung Disease Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, , London, UK.
Thorax (Impact Factor: 8.29). 01/2013; 68(5). DOI: 10.1136/thoraxjnl-2012-201786
Source: PubMed


Background A polymorphism (rs35705950) 3 kb upstream of MUC5B, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population.
Methods Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis.
Results A significant association of the MUC5B promoter single nucleotide polymorphism with IPF (p=2.04×10–17; OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The MUC5B variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF.
Conclusions We confirm the MUC5B variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.

Download full-text


Available from: Anne-Marie Russell, Jul 16, 2015
29 Reads
  • Source
    • "This hypothesis was tested with three independent studies that investigated the MUC5B SNP rs35705950 risk allele for IPF in SSc-ILD. There was no association with SSc-ILD, while the association with IPF was confirmed by all groups (Peljto et al., 2012; Borie et al., 2013; Stock et al., 2013). This result further highlights the differences in pathogenic mechanisms associated with IPF and SSc-ILD, even when the disease tissue gene expression profiles may be similar. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic studies of human diseases have identified multiple genetic risk loci for various fibrotic diseases. This has provided insights into the myriad of biological pathways potentially involved in disease pathogenesis. These discoveries suggest that alterations in immune responses, barrier function, metabolism and telomerase activity may be implicated in the genetic risks for fibrotic diseases. In addition to genetic disease-risks, the identification of genetic disease-modifiers associated with disease complications, severity or prognosis provides crucial insights into the biological processes implicated in disease progression. Understanding the biological processes driving disease progression may be critical to delineate more effective strategies for therapeutic interventions. This review provides an overview of current knowledge and gaps regarding genetic disease-risks and genetic disease-modifiers in human fibrotic diseases.
    Frontiers in Pharmacology 12/2013; 4:159. DOI:10.3389/fphar.2013.00159 · 3.80 Impact Factor
  • Thorax 01/2013; 68(5). DOI:10.1136/thoraxjnl-2012-202957 · 8.29 Impact Factor
  • Revue des Maladies Respiratoires Actualites 04/2013; 5(2):63-69. DOI:10.1016/S1877-1203(13)70361-6
Show more