☆ 4.8 Article

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Journal

NEW ENGLAND JOURNAL OF MEDICINE

Volume 379, Issue 23, Pages 2209-2219

Publisher

MASSACHUSETTS MEDICAL SOC

DOI: 10.1056/NEJMoa1801562

Keywords

Funding

Societe Francaise de Rhumatologie
Fondation Arthritis
Departement Hospitalo-Universitaire Fibrose Inflammation Remodelage
National Heart, Lung, and Blood Institute [UH2/3-HL123442, R01-HL097163, R21/R33-HL120770, P01-HL092870, K23-HL138131]
National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23-AR051461]
National Institute of Allergy and Infectious Diseases [U01AI101981]
U.S. Department of Defense [W81XWH-17-1-0597]
National Center for Advancing Translational Science [UCSF-CTI KL2TR000143]
Nina Ireland Program for Lung Health
Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services [AG000949-02]
Japanese Society for the Promotion of Science

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Abstract

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 = 9.7x10(-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 = 4.7x10(-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 = 1.3x10(-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 = 7.4x10(-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 = 2.5x10(-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.

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MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Pierre-Antoine Juge, Joshua J. Solomon, Coline H. M. van Moorsel, Romain Garofoli, Joyce S. Lee, Fabienne Louis-Sydney, Jorge Rojas-Serrano, Montserrat Gonzalez-Perez, Mayra Mejia, Ivette Buendia-Roldan, Ramces Falfan-Valencia, Enrique Ambrocio-Ortiz, Effrosyni Manali, Spyros A. Papiris, Theofanis Karageorgas, Dimitrios Boumpas, Katarina M. Antoniou, Prodromos Sidiropoulos, Athina Trachalaki, Joanne J. Van der Vis, Anna Jamnitski, Jan C. Grutters, Caroline Kannengiesser, Raphael Borie, Leticia Kawano-Dourado, Lidwine Wemeau-Stervinou, Rene-Marc Flipo, Hilario Nunes, Yurdagul Uzunhan, Dominique Valeyre, Nathalie Saidenberg-Kermanac'h, Marie-Christophe Boissier, Christophe Richez, Thierry Schaeverbeke, Tracy Doyle, Paul J. Wolters, Marie-Pierre Debray, Catherine Boileau, Raphael Porcher, David A. Schwartz, Bruno Crestani, Philippe Dieude

Summary: The study found that the MUC5B rs35705950 variant does not impact lung transplant-free survival or decline in pulmonary function in patients with RA-ILD, regardless of the HRCT pattern.

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