TY - JOUR
TI - MUC5B promoter variant and rheumatoid arthritis with interstitial lung disease
AU - Juge, P.-A.
AU - Lee, J.S.
AU - Ebstein, E.
AU - Furukawa, H.
AU - Dobrinskikh, E.
AU - Gazal, S.
AU - Kannengiesser, C.
AU - Ottaviani, S.
AU - Oka, S.
AU - Tohma, S.
AU - Tsuchiya, N.
AU - Rojas-Serrano, J.
AU - González-Pérez, M.I.
AU - Mejía, M.
AU - Buendía-Roldán, I.
AU - Falfán-Valencia, R.
AU - Ambrocio-Ortiz, E.
AU - Manali, E.
AU - Papiris, S.A.
AU - Karageorgas, T.
AU - Boumpas, D.
AU - Antoniou, K.
AU - Van Moorsel, C.H.M.
AU - Van Der Vis, J.
AU - De Man, Y.A.
AU - Grutters, J.C.
AU - Wang, Y.
AU - Borie, R.
AU - Wemeau-Stervinou, L.
AU - Wallaert, B.
AU - Flipo, R.-M.
AU - Nunes, H.
AU - Valeyre, D.
AU - Saidenberg-Kermanac'H, N.
AU - Boissier, M.-C.
AU - Marchand-Adam, S.
AU - Frazier, A.
AU - Richette, P.
AU - Allanore, Y.
AU - Sibilia, J.
AU - Dromer, C.
AU - Richez, C.
AU - Schaeverbeke, T.
AU - Lioté, H.
AU - Thabut, G.
AU - Nathan, N.
AU - Amselem, S.
AU - Soubrier, M.
AU - Cottin, V.
AU - Clément, A.
AU - Deane, K.
AU - Walts, A.D.
AU - Fingerlin, T.
AU - Fischer, A.
AU - Ryu, J.H.
AU - Matteson, E.L.
AU - Niewold, T.B.
AU - Assayag, D.
AU - Gross, A.
AU - Wolters, P.
AU - Schwarz, M.I.
AU - Holers, M.
AU - Solomon, J.J.
AU - Doyle, T.
AU - Rosas, I.O.
AU - Blauwendraat, C.
AU - Nalls, M.A.
AU - Debray, M.-P.
AU - Boileau, C.
AU - Crestani, B.
AU - Schwartz, D.A.
AU - Dieudé, P.
JO - The New England journal of medicine
PY - 2018
VL - 379
TODO - 23
SP - 2209-2219
PB - Massachussetts Medical Society
SN - null
TODO - 10.1056/NEJMoa1801562
TODO - 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
TODO - 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.
ER -