학술논문
MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease
Document Type
article
Author
Juge, Pierre-Antoine; Lee, Joyce S; Ebstein, Esther; Furukawa, Hiroshi; Dobrinskikh, Evgenia; Gazal, Steven; Kannengiesser, Caroline; Ottaviani, Sébastien; Oka, Shomi; Tohma, Shigeto; Tsuchiya, Naoyuki; Rojas-Serrano, Jorge; González-Pérez, Montserrat I; Mejía, Mayra; Buendía-Roldán, Ivette; Falfán-Valencia, Ramcés; Ambrocio-Ortiz, Enrique; Manali, Effrosyni; Papiris, Spyros A; Karageorgas, Theofanis; Boumpas, Dimitrios; Antoniou, Katarina; van Moorsel, Coline HM; van der Vis, Joanne; de Man, Yaël A; Grutters, Jan C; Wang, Yaping; Borie, Raphaël; Wemeau-Stervinou, Lidwine; Wallaert, Benoît; Flipo, René-Marc; Nunes, Hilario; Valeyre, Dominique; Saidenberg-Kermanac’h, Nathalie; Boissier, Marie-Christophe; Marchand-Adam, Sylvain; Frazier, Aline; Richette, Pascal; Allanore, Yannick; Sibilia, Jean; Dromer, Claire; Richez, Christophe; Schaeverbeke, Thierry; Lioté, Huguette; Thabut, Gabriel; Nathan, Nadia; Amselem, Serge; Soubrier, Martin; Cottin, Vincent; Clément, Annick; Deane, Kevin; Walts, Avram D; Fingerlin, Tasha; Fischer, Aryeh; Ryu, Jay H; Matteson, Eric L; Niewold, Timothy B; Assayag, Deborah; Gross, Andrew; Wolters, Paul; Schwarz, Marvin I; Holers, Michael; Solomon, Joshua J; Doyle, Tracy; Rosas, Ivan O; Blauwendraat, Cornelis; Nalls, Mike A; Debray, Marie-Pierre; Boileau, Catherine; Crestani, Bruno; Schwartz, David A; Dieudé, Philippe
Source
New England Journal of Medicine. 379(23)
Subject
Language
Abstract
BackgroundGiven 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.MethodsUsing 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.ResultsAnalysis 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.ConclusionsWe 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.).