1. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease
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Yaping Wang, Annick Clement, Nadia Nathan, Joanne J. van der Vis, Huguette Lioté, Aryeh Fischer, Dominique Valeyre, David A. Schwartz, Jan C. Grutters, Timothy B Niewold, Michael A. Nalls, Ivette Buendía-Roldán, Dimitrios Boumpas, Vincent Cottin, Marie-Christophe Boissier, Theofanis Karageorgas, Mayra Mejía, Yaël A de Man, Kevin D. Deane, Effrosyni D. Manali, Katarina M. Antoniou, Joshua J. Solomon, Jay H. Ryu, Pierre-Antoine Juge, Martin Soubrier, Jean Sibilia, Hilario Nunes, Marie-Pierre Debray, Christophe Richez, Spyros Papiris, Steven Gazal, Catherine Boileau, Deborah Assayag, Nathalie Saidenberg-Kermanac’h, Tasha E. Fingerlin, Claire Dromer, Marvin I. Schwarz, Esther Ebstein, Michael Holers, Tracy J. Doyle, Ivan O. Rosas, Bruno Crestani, Hiroshi Furukawa, Evgenia Dobrinskikh, Cornelis Blauwendraat, Paul J. Wolters, Naoyuki Tsuchiya, Thierry Schaeverbeke, Ramcés Falfán-Valencia, Lidwine Wemeau-Stervinou, Gabriel Thabut, Shigeto Tohma, Coline H.M. van Moorsel, Montserrat I González-Pérez, Andrew J. Gross, Benoit Wallaert, Shomi Oka, Caroline Kannengiesser, Joyce S. Lee, Enrique Ambrocio-Ortiz, Aline Frazier, Sylvain Marchand-Adam, René-Marc Flipo, Eric L. Matteson, Pascal Richette, S. Amselem, Raphael Borie, Jorge Rojas-Serrano, Yannick Allanore, Sébastien Ottaviani, Philippe Dieudé, Avram D Walts, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Colorado School of Medicine, Université de Tsukuba = University of Tsukuba, Sagamihara National Hospital [Kanagawa, Japan], Harvard T.H. Chan School of Public Health, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Athens, 'Attikon' Hospital, National and Kapodistrian University of Athens (NKUA), University of Crete [Heraklion] (UOC), St. Antonius Hospital [Nieuwegein], Nanjing Medical University, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Avicenne [AP-HP], Physiopathologie, Cibles et Thérapies de la Polyarthrite Rhumatoïde, Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Lariboisière-Fernand-Widal [APHP], Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA), CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), National Jewish Health (NJH), Mayo Clinic and Mayo College of Medicine, Rochester, New York University School of Medicine, NYU System (NYU), McGill University = Université McGill [Montréal, Canada], University of California [San Francisco] (UC San Francisco), University of California (UC), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris FranceFondation Arthritis, Département Hospitalo-Universitaire Fibrose Inflammation Remodelage, National Heart, Lung, and Blood Institute (UH2/3-HL123442, R01-HL097163, R21/R33-HL120770, P01-HL092870, and K23-HL138131), National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23-AR051461), National Institute of Allergy and Infectious Diseases (U01-AI101981), U.S. Department of Defense (W81XWH-17-1-0597), National Center for Advancing Translational Science (UCSF-CTI KL2TR000143), the Nina Ireland Program for Lung Health, the Intramural Research Program of the National Institute of Aging, part of the National Institutes of Health, Department of Health and Human Services (Z01-AG000949–02), and the Japanese Society for the Promotion of Science., Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), and Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris France
- Subjects
Male ,Lung Diseases ,medicine.medical_specialty ,Genotype ,[SDV]Life Sciences [q-bio] ,Population ,Arthritis ,behavioral disciplines and activities ,Gastroenterology ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Promoter Regions ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Genetic ,Internal medicine ,Gain of Function Mutation ,Odds Ratio ,Medicine ,Humans ,Genetic Predisposition to Disease ,Rheumatoid/complications/*genetics ,Risk factor ,education ,Aged ,030203 arthritis & rheumatology ,Lung/chemistry/pathology ,education.field_of_study ,business.industry ,Interstitial lung disease ,General Medicine ,Odds ratio ,respiratory system ,Middle Aged ,medicine.disease ,respiratory tract diseases ,3. Good health ,body regions ,Minor allele frequency ,030228 respiratory system ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Rheumatoid arthritis ,Female ,Interstitial/complications/*genetics ,Mucin-5B/analysis/*genetics ,business ,Idiopathic Pulmonary Fibrosis/genetics - Abstract
International audience; 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.).
- Published
- 2018
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