MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease - Université Claude Bernard Lyon 1 Access content directly
Journal Articles New England Journal of Medicine Year : 2018

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

Pierre-Antoine Juge (1, 2) , Joyce S. Lee (3) , Esther Ebstein (1) , Hiroshi Furukawa (4, 5) , Evgenia Dobrinskikh (3) , Steven Gazal (6, 7) , Caroline Kannengiesser (1, 2) , Sebastien Ottaviani (1) , Shomi Oka (5, 4) , Shigeto Tohma (5) , Naoyuki Tsuchiya (4) , Jorge Rojas-Serrano , Montserrat I. Gonzalez-Perez , Mayra Mejia , Ivette Buendia-Roldan , Ramces Falfan-Valencia , Enrique Ambrocio-Ortiz , Effrosyni Manali (8, 9) , Spyros A. Papiris (8, 9) , Theofanis Karageorgas (8, 9) , Dimitrios Boumpas (8, 9) , Katarina Antoniou (10) , Coline H. M. van Moorsel (11) , Joanne van der Vis (11) , Yael A. de Man (11) , Jan C. Grutters (11) , Yaping Wang (12) , Raphael Borie (1, 2) , Lidwine Wemeau-Stervinou (13) , Benoit Wallaert (13) , René-Marc Flipo (13) , Hilario Nunes (14) , Dominique Valeyre (14) , Nathalie Saidenberg-Kermanac'H (14, 15) , Marie-Christophe Boissier (14, 15) , Sylvain Marchand-Adam (16) , Aline Frazier (17) , Pascal Richette (17, 18) , Yannick Allanore (19, 20) , Jean Sibilia (21, 22, 23) , Claire Dromer (24) , Christophe Richez (24, 25) , Thierry Schaeverbeke (24, 25) , Huguette Liote (26) , Gabriel Thabut (1, 2) , N. Nathan (27, 28) , S. Amselem (27, 28) , M. Soubrier (29, 30) , Vincent Cottin (31, 32) , Annick Clement (27, 28) , Kevin Deane (3) , Avram D. Walts (3) , Tasha Fingerlin (33) , Aryeh Fischer (3) , Jay H. Ryu (34) , Eric L. Matteson (34) , Timothy B. Niewold (35) , Deborah Assayag (36) , Andrew Gross (37) , Paul Wolters (37) , Marvin I. Schwarz (3) , Michael Holers (3) , Joshua J. Solomon (33) , Tracy Doyle (38) , Ivan O. Rosas (38) , Cornelis Blauwendraat (39) , Mike A. Nalls (39) , Marie-Pierre Debray (1) , Catherine Boileau (1) , Bruno Crestani (1, 2) , David A. Schwartz (3) , P. Dieude (2, 1)
1 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
2 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
3 University of Colorado School of Medicine
4 Université de Tsukuba = University of Tsukuba
5 Sagamihara National Hospital [Kanagawa, Japan]
6 Harvard T.H. Chan School of Public Health
7 BROAD INSTITUTE - Broad Institute of MIT and Harvard
8 “Attikon” University Hospital
9 NKUA - National and Kapodistrian University of Athens
10 UOC - University of Crete [Heraklion]
11 St. Antonius Hospital [Nieuwegein]
12 Nanjing Medical University
13 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
14 Hôpital Avicenne [AP-HP]
15 Physiopathologie, Cibles et Thérapies de la Polyarthrite Rhumatoïde
16 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
17 Hôpital Lariboisière-Fernand-Widal [APHP]
18 BIOSCAR (UMR_S_1132 / U1132) - Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques
19 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
20 IC UM3 (UMR 8104 / U1016) - Institut Cochin
21 Hôpital de Hautepierre [Strasbourg]
22 Immuno-Rhumatologie Moléculaire
23 UNISTRA - Université de Strasbourg
24 CHU Bordeaux
25 ImmunoConcept - Immunology from Concept and Experiments to Translation
26 CHU Tenon [AP-HP]
27 U933 - Maladies génétiques d'expression pédiatrique
28 CHU Trousseau [APHP]
29 CHU Clermont-Ferrand
30 UNH - Unité de Nutrition Humaine
31 IVPC - Infections Virales et Pathologie Comparée - UMR 754
32 Hôpital Louis Pradel [CHU - HCL]
33 NJH - National Jewish Health
34 Mayo Clinic and Mayo College of Medicine
35 New York University School of Medicine
36 McGill University = Université McGill [Montréal, Canada]
37 UC San Francisco - University of California [San Francisco]
38 BWH - Brigham & Women’s Hospital [Boston]
39 NIA - National Institute on Aging [Bethesda, USA]
Joyce S. Lee
  • Function : relator_co_first_author
Jorge Rojas-Serrano
  • Function : Author
Montserrat I. Gonzalez-Perez
  • Function : Author
Mayra Mejia
  • Function : Author
Ivette Buendia-Roldan
  • Function : Author
Ramces Falfan-Valencia
  • Function : Author
Enrique Ambrocio-Ortiz
  • Function : Author
Claire Dromer
  • Function : Author
Huguette Liote
  • Function : Author
M. Soubrier

Abstract

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. (Funded by Societe Francaise de Rhumatologie and others.).

Dates and versions

hal-02191891 , version 1 (23-07-2019)

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Pierre-Antoine Juge, Joyce S. Lee, Esther Ebstein, Hiroshi Furukawa, Evgenia Dobrinskikh, et al.. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease. New England Journal of Medicine, 2018, 379 (23), pp.2209-2219. ⟨10.1056/NEJMoa1801562⟩. ⟨hal-02191891⟩
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