MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

作者：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.; Gonzalez-Perez, M. I.; Mejia, M.; Buendia-Roldan, I.; Falfan-Valencia, R.; Ambrocio-Ortiz, E.; M****i, 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.

来源：New England Journal of Medicine, 2018, 379(23): 2209-2219.

DOI：10.1056/NEJMoa1801562

• IDIOPATHIC PULMONARY-FIBROSIS
• POLYMORPHISM
• ASSOCIATION
• MORTALITY
• SUSCEPTIBILITY
• CLASSIFICATION
• PREDICTORS
• PNEUMONIA
• CRITERIA
• COHORT

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 = 9.7x10(-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 = 4.7x10(-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 = 1.3x10(-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 = 7.4x10(-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 = 2.5x10(-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.

• 出版日期2018-12-6
• 单位南京大学