Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
Carmona, F. David (Universidad de Granada)
Coit, Patrick (University of Michigan)
Saruhan-Direskeneli, Güher (Department of Physiology, Istanbul Medical Faculty, Istanbul University)
Hernández-Rodríguez, José (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Cid, María Cinta (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Solans, Roser (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Castañeda, Santos (Instituto de Investigación Hospital Universitario de la Princesa)
Vaglio, Augusto (University Hospital of Parma)
Direskeneli, Haner (Marmara University)
Merkel, Peter A. (University of Pennsylvania)
Boiardi, Luigi (Istituto di Ricovero e Cura a Carattere Scientifico)
Salvarani, Carlo (Istituto di Ricovero e Cura a Carattere Scientifico)
Gonzalez-Gay, MA (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Martín, Javier (Universidad de Granada)
Sawalha, Amr H. (University of Michigan)
Universitat Autònoma de Barcelona

Data:	2017
Resum:	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 = 1. 19, OR = 1. 50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P = 5. 52E-04, OR = 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.
Ajuts:	Ministerio de Economía y Competitividad SAF2012-34435 Ministerio de Economía y Competitividad RD12/0009/0004 Ministerio de Economía y Competitividad RYC-2014-16458 Ministerio de Economía y Competitividad SAF14/57708R Ministerio de Economía y Competitividad PIE13/00033
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Scientific reports, Vol. 7 (03 2017) , ISSN 2045-2322

DOI: 10.1038/srep43953
PMID: 28277489

10 p, 975.3 KB

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