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