OP0284 Muc5b promoter variant rs35705950 is a risk factor for rheumatoid arthritis – interstitial lung disease. (12th June 2018)

• Record Type: Journal Article
• Authors: Juge, P.-A.; Lee, J.S.; Ebstein, E.; Furukawa, H.; Dobrinskikh, E.; Gazal, S.; Kannengiesser, C.; Ottaviani, S.; Tsuchiya, N.; Oka, S.; Tohma, S.; Rojas-Serrano, J.; Gonzalez-Perez, M.-I.; Mejia, M.; Buendia-Roldan, I.; Falfan-Valencia, R.; Manali, E.; Papiris, S.A.; Karageorgas, T.; Boumpas, D.; Antoniou, K.; Van Moorsel, C.; van der Vis, J.; de Man, Y.; Grutters, J.; Wang, Y.; Borie, R.; Wemeau-Stervinou, L.; Wallaert, B.; Flipo, R.-M.; Nunes, H.; Valeyre, D.; Saidenberg, N.; Marchand-Adam, S.; Deane, K.; Walts, A.; Fingerlin, T.; Matteson, E.; Niewold, T.; Assayag, D.; Gross, A.; Wolters, P.; Schwarz, M.; Holers, M.; Solomon, J.; Doyle, T.; Debray, M.-P.; Boileau, C.; Crestani, B.; Schwartz, D.; Dieudé, P.;
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 190
• Page End: 190
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.4727
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) share phenotypic similarities. The gain-of-function MUC5B promoter variant rs35705950 is the strongest risk factor for development of IPF Objectives: We hypothesised that rs35705950 would also contribute to the risk of ILD in RA patients. Methods: Using a French discovery population and multi-ethnic validation populations from 6 different countries, we tested the association of the MUC5B promoter variant in RA-ILD (n=620), RA without ILD (n=614), and unaffected controls (n=5448). Results: The discovery population revealed an association of the MUC5B promoter variant with RA-ILD when compared to unaffected controls (ORadj =3.8 95% CI: 2.8 to 5.2; p=9.7x10–1 7 ) (figure 1A). Similar to the discovery cohort, the MUC5B promoter variant was significantly over-represented among the cases of RA-ILD in the multi-ethnic study cohorts when compared to unaffected controls (OR adj =5.5 95% CI: 4.2 to 7.2; p=4.7x10–3 5 ) (figure 1A), and when the discovery population and the multi-ethnic cohorts were combined (OR combined =4.7 95% CI: 3.9 to 5.8; p=1.3x10–4 9 ) (figure 1A). Additionally, the MUC5B promoter variant was found to increase the risk of ILD among patients with RA (OR combined =3.1 95% CI: 1.8 to 5.4; p=7.4x10–5), however, no statistical association with the MUC5B promoter variant was observed for RA without ILD (figure 1B). The association of the MUC5B promoter variant with RA-ILD increased significantly when restricted to the usual interstitial pneumonia (UIP) by high-resolution computed tomography (OR combined =6.1 95% CI: 2.9 to 13.1; p=2.5x10–6) (figure 1C). Immunohistochemical and in-situ hybridization analysis of RA-ILD lung tissue demonstrated expression of MUC5B by type 2 alveolar epithelial cells undergoing endoplasmic reticulum stress. Conclusions: Our findings demonstrate that MUC5B promoter variant rs35705950 is a risk factor for RA-ILD specifically associated with radiologic evidence of UIP. Disclosure of Interest: None declared