학술논문
MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression
Document Type
article
Author
Juge, Pierre-Antoine; Solomon, Joshua J; van Moorsel, Coline HM; Garofoli, Romain; Lee, Joyce S; Louis-Sydney, Fabienne; Rojas-Serrano, Jorge; González-Pérez, Montserrat I; Mejia, Mayra; Buendia-Roldán, Ivette; Falfán-Valencia, Ramcés; Ambrocio-Ortiz, Enrique; Manali, Effrosyni; Papiris, Spyros A; Karageorgas, Theofanis; Boumpas, Dimitrios; Antoniou, Katarina M; Sidiropoulos, Prodromos; Trachalaki, Athina; van der Vis, Joanne J; Jamnitski, Anna; Grutters, Jan C; Kannengiesser, Caroline; Borie, Raphaël; Kawano-Dourado, Leticia; Wemeau-Stervinou, Lidwine; Flipo, René-Marc; Nunes, Hilario; Uzunhan, Yurdagul; Valeyre, Dominique; Saidenberg-Kermanac'h, Nathalie; Boissier, Marie-Christophe; Richez, Christophe; Schaeverbeke, Thierry; Doyle, Tracy; Wolters, Paul J; Debray, Marie-Pierre; Boileau, Catherine; Porcher, Raphaël; Schwartz, David A; Crestani, Bruno; Dieudé, Philippe
Source
Seminars in Arthritis and Rheumatism. 51(5)
Subject
Language
Abstract
BackgroundThe major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD.MethodsThrough an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline.ResultsOut of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern.ConclusionIn this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.