MUC5B promoter variant and rheumatoid arthritis with interstitial lung disease

P. A. Juge, J. S. Lee, E. Ebstein, H. Furukawa, E. Dobrinskikh, S. Gazal, C. Kannengiesser, S. Ottaviani, S. Oka, S. Tohma, N. Tsuchiya, J. Rojas-Serrano, M. I. González-Pérez, M. Mejía, I. Buendía-Roldán, R. Falfán-Valencia, E. Ambrocio-Ortiz, E. Manali, S. A. Papiris, T. KarageorgasD. Boumpas, K. Antoniou, C. H.M. Van Moorsel, J. Van Der Vis, Y. A. De Man, J. C. Grutters, Y. Wang, R. Borie, L. Wemeau-Stervinou, B. Wallaert, R. M. Flipo, H. Nunes, D. Valeyre, N. Saidenberg-Kermanac'H, M. C. Boissier, S. Marchand-Adam, A. Frazier, P. Richette, Y. Allanore, J. Sibilia, C. Dromer, C. Richez, T. Schaeverbeke, H. Lioté, G. Thabut, N. Nathan, S. Amselem, M. Soubrier, V. Cottin, A. Clément, K. Deane, A. D. Walts, T. Fingerlin, A. Fischer, J. H. Ryu, E. L. Matteson, T. B. Niewold, D. Assayag, A. Gross, P. Wolters, M. I. Schwarz, M. Holers, J. J. Solomon, T. Doyle, I. O. Rosas, C. Blauwendraat, M. A. Nalls, M. P. Debray, C. Boileau, B. Crestani, D. A. Schwartz, P. Dieudé

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

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 = 9.7×10-17). 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.

Original languageEnglish (US)
Pages (from-to)2209-2219
Number of pages11
JournalNew England Journal of Medicine
Volume379
Issue number23
DOIs
StatePublished - Dec 6 2018

ASJC Scopus subject areas

  • General Medicine

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