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

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; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Sci Rep.2017 Mar 9;7:43953

Editorial: Nature Publishing Group

 Año de publicación: 2017

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/srep43953

ISSN: 2045-2322

Autores/as

CARMONA, F. DAVID

COIT, PATRICK

SARUHAN-DIRESKENELI, GÜHER

HERNÁNDEZ RODRÍGUEZ, JOSÉ

CID, MARÍA C.

SOLANS, ROSER

CASTAÑEDA, SANTOS

VAGLIO, AUGUSTO

DIRESKENELI, HANER

MERKEL, PETER A.

BOIARDI, LUIGI

SALVARANI, CARLO

SPANISH GCA STUDY GROUP

ITALIAN GCA STUDY GROUP

TURKISH TAKAYASU STUDY GROUP

VASCULITIS CLINICAL RESEARCH CONSORTIUM