/ / EN
JOINT WEBSITE OF THE HONG KONG THORACIC SOCIETY AND THE CHEST DELEGATION HONG KONG AND MACAU
back to home

New England Journal of Medicine

2018 Dec 6 - MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

Pierre-Antoine Juge, M.D., Joyce S. Lee, M.D., Esther Ebstein, M.D., Hiroshi Furukawa, M.D., Ph.D., Evgenia Dobrinskikh, Ph.D., Steven Gazal, Ph.D., Caroline Kannengiesser, Pharm.D., Ph.D., Sébastien Ottaviani, M.D., Shomi Oka, Ph.D., Shigeto Tohma, M.D., Naoyuki Tsuchiya, M.D., Ph.D., Jorge Rojas-Serrano, M.D., Ph.D., Montserrat I. González-Pérez, M.D., Mayra Mejía, M.D., Ivette Buendía-Roldán, M.D., Ramcés Falfán-Valencia, Ph.D., Enrique Ambrocio-Ortiz, M.D., Effrosyni Manali, M.D., Ph.D., Spyros A. Papiris, M.D., Ph.D., Theofanis Karageorgas, M.D., Ph.D., Dimitrios Boumpas, M.D., Ph.D., Katarina Antoniou, M.D., Ph.D., Coline H.M. van Moorsel, Ph.D., Joanne van der Vis, B.Sc., Yaël A. de Man, M.D., Ph.D., Jan C. Grutters, M.D., Ph.D., Yaping Wang, M.D., Raphaël Borie, M.D., Ph.D., Lidwine Wemeau-Stervinou, M.D., Benoît Wallaert, M.D., Ph.D., René-Marc Flipo, M.D., Ph.D., Hilario Nunes, M.D., Ph.D., Dominique Valeyre, M.D., Ph.D., Nathalie Saidenberg-Kermanac’h, M.D., Ph.D., Marie-Christophe Boissier, M.D., Ph.D., Sylvain Marchand-Adam, M.D., Ph.D., Aline Frazier, M.D., Pascal Richette, M.D., Ph.D., Yannick Allanore, M.D., Ph.D., Jean Sibilia, M.D., Ph.D., Claire Dromer, M.D., Ph.D., Christophe Richez, M.D., Ph.D., Thierry Schaeverbeke, M.D., Ph.D., Huguette Lioté, M.D., Gabriel Thabut, M.D., Ph.D., Nadia Nathan, M.D., Serge Amselem, M.D., Ph.D., Martin Soubrier, M.D., Ph.D., Vincent Cottin, M.D., Ph.D., Annick Clément, M.D., Ph.D., Kevin Deane, M.D., Ph.D., Avram D. Walts, M.S., Tasha Fingerlin, Ph.D., Aryeh Fischer, M.D., Jay H. Ryu, M.D., Eric L. Matteson, M.D., M.P.H., Timothy B. Niewold, M.D., Deborah Assayag, M.D., Andrew Gross, M.D., Paul Wolters, M.D., Marvin I. Schwarz, M.D., Michael Holers, M.D., Ph.D., Joshua J. Solomon, M.D., Tracy Doyle, M.D., Ivan O. Rosas, M.D., Cornelis Blauwendraat, Ph.D., Mike A. Nalls, Ph.D., Marie-Pierre Debray, M.D., Catherine Boileau, Pharm.D., Ph.D., Bruno Crestani, M.D., Ph.D., David A. Schwartz, M.D., and Philippe Dieudé, M.D., Ph.D.

N Engl J Med 2018; 379:2209-2219


BACKGROUND
Given the phenotypic similarities between rheumatoid arthritis (RA)–associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA.

METHODS
Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls.

RESULTS
Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10−17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10−35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10−49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10−5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10−6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone.

CONCLUSIONS
We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.)


Weblink here
Top