@article{3106724,
    title = "MUC5B promoter variant and rheumatoid arthritis with interstitial lung disease",
    author = "Juge, P.-A. and Lee, J.S. and Ebstein, E. and Furukawa, H. and Dobrinskikh, E. and Gazal, S. and Kannengiesser, C. and Ottaviani, S. and Oka, S. and Tohma, S. and Tsuchiya, N. and Rojas-Serrano, J. and González-Pérez, M.I. and Mejía, M. and Buendía-Roldán, I. and Falfán-Valencia, R. and Ambrocio-Ortiz, E. and Manali, E. and Papiris, S.A. and Karageorgas, T. and Boumpas, D. and Antoniou, K. and Van Moorsel, C.H.M. and Van Der Vis, J. and De Man, Y.A. and Grutters, J.C. and Wang, Y. and Borie, R. and Wemeau-Stervinou, L. and Wallaert, B. and Flipo, R.-M. and Nunes, H. and Valeyre, D. and Saidenberg-Kermanac'H, N. and Boissier, M.-C. and Marchand-Adam, S. and Frazier, A. and Richette, P. and Allanore, Y. and Sibilia, J. and Dromer, C. and Richez, C. and Schaeverbeke, T. and Lioté, H. and Thabut, G. and Nathan, N. and Amselem, S. and Soubrier, M. and Cottin, V. and Clément, A. and Deane, K. and Walts, A.D. and Fingerlin, T. and Fischer, A. and Ryu, J.H. and Matteson, E.L. and Niewold, T.B. and Assayag, D. and Gross, A. and Wolters, P. and Schwarz, M.I. and Holers, M. and Solomon, J.J. and Doyle, T. and Rosas, I.O. and Blauwendraat, C. and Nalls, M.A. and Debray, M.-P. and Boileau, C. and Crestani, B. and Schwartz, D.A. and Dieudé, P.",
    journal = "The New England journal of medicine",
    year = "2018",
    volume = "379",
    number = "23",
    pages = "2209-2219",
    publisher = "Massachussetts Medical Society",
    doi = "10.1056/NEJMoa1801562",
    keywords = "mucin 5B;  mucin 5B, adult;  aged;  Article;  case study;  computer assisted tomography;  controlled study;  disease course;  female;  gain of function mutation;  gene expression;  gene frequency;  genetic association;  genetic variability;  genotype;  human;  human tissue;  interstitial lung disease;  interstitial pneumonia;  lung parenchyma;  major clinical study;  male;  middle aged;  MUC5B gene;  patient risk;  priority journal;  promoter region;  rheumatoid arthritis;  risk factor;  single nucleotide polymorphism;  validation study;  chemistry;  complication;  fibrosing alveolitis;  gain of function mutation;  genetic predisposition;  genetics;  interstitial lung disease;  lung;  odds ratio;  pathology;  promoter region;  rheumatoid arthritis, Aged;  Arthritis, Rheumatoid;  Female;  Gain of Function Mutation;  Genetic Predisposition to Disease;  Genotype;  Humans;  Idiopathic Pulmonary Fibrosis;  Lung;  Lung Diseases, Interstitial;  Male;  Middle Aged;  Mucin-5B;  Odds Ratio;  Promoter Regions, Genetic",
    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. Copyright © 2018 Massachusetts Medical Society."
}