Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis
In: PLoS Genetics PLoS Genetics, 2011, 7 (7), pp.e1002091. ⟨10.1371/journal.pgen.1002091⟩ PLoS Genetics, Public Library of Science, Jg. 7 (2011-07-01), Heft 7, p e1002091
Online
unknown
Zugriff:
Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P
Author Summary Systemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy, severe immunologic alterations, and massive deposits of matrix components in the connective tissue. Epidemiological investigations indicate that SSc follows a pattern of multifactorial inheritance; however, only a few loci have been replicated in multiple studies. We undertook a two-stage genome-wide association study of SSc involving over 8,800 individuals of European ancestry. Combined analyses showed independent association at the known HLA-DQB1 region and revealed associations at PSORS1C1, TNIP1, and RHOB loci, in agreement with a strong immune genetic component. Because of its biological relevance, and previous reports of genetic association at this locus with other connective tissue disorders, we investigated TNIP1 expression. We observed a markedly reduced expression of the gene and its protein product in SSc, as well as its potential implication in control of extra-cellular matrix synthesis, providing a new clue for a link between inflammation/immunity and fibrosis.
| Titel: |
Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis
|
|---|---|
| Autor/in / Beteiligte Person: | Riccieri, Valeria ; Czirják, László ; Allanore, Yannick ; Cracowski, Jean-Luc ; Boileau, Catherine ; Melchers, Inga ; Wichmann, H.-Erich ; Lambert, Jean-Charles ; Meyer, Oliver ; Wipff, Julien ; Saad, Mohamad ; Jörg H W Distler ; Mouthon, Luc ; Anne Marie Dupuy ; Conti, Costanza ; Müller, Martina ; Hunzelmann, Nicolas ; Martinez, Maria ; Matucci-Cerinic, Marco ; Diot, Elisabeth ; Müller-Ladner, Ulf ; Caramaschi, Paola ; Kowal-Bielecka, Otylia ; Kahan, André ; Salvi, Erika ; Riemekasten, G. ; Munnich, Arnold ; Airò, Paolo ; Letenneur, Luc ; Hachulla, Eric ; Tiev, Kiet ; Ruiz, Barbara ; Cusi, Daniele ; Avouac, Jérôme ; Damjanov, Nemanja ; Dieudé, Philippe ; Valentini, Gabriele ; Amouyel, Philippe ; Service de rhumatologie [CHU Cochin] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; 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) ; Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Centre de Physiopathologie Toulouse Purpan (CPTP) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Service de Rhumatologie ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité ; Immunopathologie rénale, récepteurs et inflammation ; Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Department of Internal Medicine 3 ; Institute for Clinical Immunology Erlangen-Nuremberg ; Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé ; Departments of Medicine, Biomedicine & Rheumatology ; Università degli Studi di Firenze = University of Florence (UniFI)-Division of Rheumatology AOUC - Denothe Centre ; Department of Rheumatology and Clinical Immunology ; Charité - UniversitätsMedizin = Charité - University Hospital [Berlin] ; Rheumatology and Clinical Immunology ; Civili, Spedali ; Clinical Research Unit for Rheumatology ; Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik) ; Service de médecine interne ; Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille) ; Department of Medicine, Surgery, and Dentistry ; University of Milano ; Genomics and Bioinformatics Platform ; Filarete, Fondazione ; Institute of Medical Informatics, Biometry, and Epidemiology ; Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology ; Institute of Epidemiology, I ; Helmholtz Zentrum München = German Research Center for Environmental Health ; Department of Dermatology ; University of Cologne ; CHU Saint-Antoine [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) ; Unit, Rheumatology ; Università degli studi di Verona = University of Verona (UNIVR) ; Pathologies Respiratoires : Protéolyse et Aérosolthérapie ; Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Department of Rheumatology and Internal Medicine ; Medical University of Białystok (MUB) ; Department of Clinical and Experimental Medicine ; University of Naples Federico II = Università degli studi di Napoli Federico, II ; Service de médecine interne et centre de référence des maladies rares [CHU Cochin] ; Department of Immunology and Rheumatology ; University of Pecs ; Institute of Rheumatology ; University of Belgrade [Belgrade] ; Kos Genetic, SRL ; Institute of Genetic Epidemiology ; Justus-Liebig-Universität Gießen = Justus Liebig University (JLU) ; Division of Rheumatology ; Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA) ; Centre d'Investigation Clinique [Grenoble] (CIC Grenoble) ; Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Epidémiologie et Biostatistique [Bordeaux] ; Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC) ; Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) ; Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP] ; This project was funded by Agence Nationale pour la Recherche (Project ANR-08-GENO-016-1) and supported by research grants from SERVIER research group, SANOFI-AVENTIS, Association des Sclérodermies de France, and Groupe Français de Recherche sur la Sclérodermie. The KORA (Cooperative health research in the Region of Augsburg) studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN). This research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. HYPERGENES (European Network for Genetic-Epidemiological Studies) is funded by EU within the FP7: HEALTH-F4-2007-201550. ; European Project: 201550,EC:FP7:HEALTH,FP7-HEALTH-2007-A,HYPERGENES(2008) ; Hôpital Cochin [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité ; Division of Rheumatology AOUC - Denothe Centre-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI) ; Freiburg University Medical Center ; German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM) ; Service de médecine interne [Saint-Antoine] ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU) ; University of Verona (UNIVR) ; Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Medical University of Bialystok ; University of Naples Federico, II ; German Research Center for Environmental Health ; Justus-Liebig-Universität Gießen (JLU) ; Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] ; Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Division of Rheumatology AOUC - Denothe Centre ; Allanore, Y ; Saad, M ; Dieudé, P ; Avouac, J ; Distler, Jh ; Amouyel, P ; MATUCCI CERINIC, M ; Riemekasten, G ; Airo, P ; Melchers, I ; Hachulla, E ; Cusi, D ; Wichmann, He ; Wipff, J ; Lambert, Jc ; Hunzelmann, N ; Tiev, K ; Caramaschi, P ; Diot, E ; KOWAL BIELECKA, O ; Mouthon, L ; Czirják, L ; Damjanov, N ; Salvi, E ; Conti, C ; Müller, M ; MÜLLER LADNER, U ; Riccieri, V ; Ruiz, B ; Cracowski, Jl ; Letenneur, L ; Dupuy, Am ; Meyer, O ; Kahan, A ; Munnich, A ; Boileau, C ; Martinez, M. ; Autard, Delphine ; European Network for Genetic-Epidemiological Studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model - HYPERGENES - - EC:FP7:HEALTH2008-01-01 - 2011-12-31 - 201550 - VALID ; Service de médecine interne [CHU Saint-Antoine] |
| Link: | |
| Zeitschrift: | PLoS Genetics PLoS Genetics, 2011, 7 (7), pp.e1002091. ⟨10.1371/journal.pgen.1002091⟩ PLoS Genetics, Public Library of Science, Jg. 7 (2011-07-01), Heft 7, p e1002091 |
| Veröffentlichung: | HAL CCSD, 2011 |
| Medientyp: | unknown |
| ISSN: | 1553-7390 (print) ; 1553-7404 (print) |
| Schlagwort: |
|
| Sonstiges: |
|