期刊
NEW ENGLAND JOURNAL OF MEDICINE
卷 379, 期 23, 页码 2209-2219出版社
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa1801562
关键词
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资金
- Societe Francaise de Rhumatologie
- Fondation Arthritis
- Departement Hospitalo-Universitaire Fibrose Inflammation Remodelage
- National Heart, Lung, and Blood Institute [UH2/3-HL123442, R01-HL097163, R21/R33-HL120770, P01-HL092870, K23-HL138131]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23-AR051461]
- National Institute of Allergy and Infectious Diseases [U01AI101981]
- U.S. Department of Defense [W81XWH-17-1-0597]
- National Center for Advancing Translational Science [UCSF-CTI KL2TR000143]
- Nina Ireland Program for Lung Health
- Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services [AG000949-02]
- Japanese Society for the Promotion of Science
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.
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