| Autor: |
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. |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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