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Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/srep43953

2045-2322

F. David Carmona, Patrick Coit, Güher Saruhan‐Direskeneli, José Hernández‐Rodríguez, María C. Cid, Roser Solans, Santos Castañeda, Augusto Vaglio, Haner Direşkeneli, Peter A. Merkel, Luigi Boiardi, Carlo Salvarani, Miguel Á. González‐Gay, Javier Martı́n, Amr H. Sawalha, Agustín Martínez-Berriochoa, Ainhoa Unzurrunzaga, Ana Hidalgo-Conde, Ana Belén Madroñero Vuelta, Antonio Fernández‐Nebro, M. Carmen Ordóñez-Cañizares, Benjamín Fernández‐Gutiérrez, Luis Rodríguez‐Rodríguez, B. Escalante, Begoña Marí-Alfonso, B. Sopeña, Carmen Gómez‐Vaquero, Enrique Raya, Elena Grau, José A. Ruiz San Román, Esther Vicente, Eugenio de Miguel, Francisco Javier López-Longo, Lina Martínez, Inmaculada C. Morado, J. Bernardino Díaz-López, Luis Caminal‐Montero, Aleida Martínez Zapico, Javier Narváez, Jordi Monfort, Laura Tío, José A. Miranda‐Filloy, Julio Sánchez-Martín, Juan José Alegre Sancho, Luis Sáez‐Comet, Mercedes Pérez-Conesa, Marc Corbera‐Bellalta, Marc Ramentol-Sintas, María Jesús García-Villanueva, Mercedes Guijarro Rojas, Norberto Ortego‐Centeno, Raquel Ríos-Fernández, José Luis Callejas‐Rubio, Olga Sánchez‐Pernaute, Patricia Fanlo Mateo, Ricardo Blanco, Sergio Prieto‐González, Victor Manuel Martínez-Taboada, Alessandra Soriano, Claudio Lunardi, Davide Gianfreda, Daniele Santilli, Francesco Bonatti, Francesco Muratore, Giulia Pazzola, Olga Addimanda, Giacomo Emmi, Giuseppe A. Ramirez, Lorenzo Beretta, Marcello Govoni, Marco A. Cimmino, Ahmet Mesut Onat, Ayşe Çefle, Ayten Yazıcı, Bünyamin Kısacık, Ediz Dalkılıç, Emire Seyahi, İzzet Fresko, Şevket Ercan Tunç, Eren Erken, Hüseyin Özer, Kenan Aksu, Gökhan Keser, Mehmet Akif Öztürk, Müge Bıçakçıgil, Nurşen Düzgün, Ömer Karadağ, Sedat Kiraz, Ömer Pamuk, Servet Akar, Fatoş Önen, Nurullah Akkoç, Sevil Kamalı, Murat İnanç, Sibel P. Yentür, Sibel Zehra Aydın, Fatma Alıbaz-Öner, Timuçin Kaşifoğlu, Veli Çobankara, Zeynep Özbalkan, Aşkın Ateş, Yaşar Karaaslan, Simon Carette, Sharon A. Chung, David Cuthbertson, Lindsay J. Forbess, Gary S. Hoffman, Nader Khalidi, Curry L. Koening, Carol A. Langford, Carol A. McAlear, Kathleen McKinnon-Maksimowicz, Paul A. Monach, Larry W. Moreland, Christian Pagnoux, Philip Seo, Robert Spiera, Antoine G. Sreih, Kenneth J. Warrington, Steven R. Ytterberg,

Systemic Lupus Erythematosus Research

Abstract Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes ( HLA-DRB1 / HLA-DQA1 ) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; OR GCA = 1.19, OR TAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P GCA = 5.52E-04, OR GCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus .