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Genetische Risikofaktoren von Vaskulitiden

Genetic risk factors for vasculitis

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Zusammenfassung

Genomweite Assoziationstudien (GWAS) sind auf dem Gebiet der Vaskulitiden bisher nur für den Morbus Behçet, das Kawasaki-Syndrom, die Granulomatose mit Polyangiitis (GPA) und die mikroskopische Polyangiitis (MPA) durchgeführt worden. Sie liefern wichtige Hinweise auf die Pathogenese und mögliche therapeutische Angriffspunkte. Mehrere GWAS weisen neben den MHC-Klasse-I-Genen HLA-B51 und HLA-A26 bestimmte Polymorphismen in Zytokin- bzw. Zytokinrezeptorgenen (IL-10 , IL-12R/IL-23R), Transkriptionsfaktoren (STAT4) und in Genen, deren Genprodukte bei der Antigenpräsentation eine Rolle spielen (ERAP-1), als genetische Risikofaktoren aus. Zwei bislang publizierte GWAS aus Europa und den USA zu den Antineutrophile-zytoplasmatische-Antikörper(ANCA)-assoziierten Vaskulitiden GPA und MPA bestätigen HLA-DP als bedeutsamsten genetischen Risikofaktor für die GPA. Die europäische GWAS bestätigt außerdem SERPINA-1, ein Defizienzallel des α-1-Antritrypsin-Gens, als Risikogen der GPA und identifiziert einen Polymorphismus im Proteinase-3(PR3)-Gen, einem der Zielantigene von ANCA, als Risikofaktor für die GPA bzw. PR3-ANCA-assoziierte Vaskulitis.

Abstract

Among the vasculitides, genome-wide association studies (GWAS) have so far been performed for Behçet’s disease, Kawasaki disease, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). These studies delivered valuable information with respect to the pathogenesis and therapeutic targets: Apart from HLA-B51 and HLA-A26, distinct polymorphisms in cytokine (IL-10) or cytokine receptor (IL-12R/IL-23R) genes, transcription factors (STAT4) and genes encoding for proteins involved in antigen presentation (ERAP-1) have been identified as risk factors for Behçet’s disease. The results of two GWAS performed for antineutrophil cytoplasmic antibody (ANCA) associated vasculitis GPA and MPA in Europe and the USA confirmed that the HLA-DP locus is the most relevant risk factor for GPA. Furthermore, the European GWAS confirmed SERPINA-1, a deficiency allele of the α-1-antitrypsin gene, as a genetic risk factor in GPA and identified a polymorphism in the proteinase 3 gene (PR3), one of the target antigens of ANCA, as a risk factor for GPA and PR3-ANCA-associated vasculitis.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. J.U. Holle und W.L. Gross geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Oskar-Alexander-Str. 26, 24576, Bad Bramstedt, Deutschland

    J.U. Holle

  2. Vaskulitiszentrum, Poliklinik für Rheumatologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland

    J.U. Holle & W.L. Gross

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  1. J.U. Holle
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Correspondence to J.U. Holle.

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Holle, J., Gross, W. Genetische Risikofaktoren von Vaskulitiden. Internist 55, 128–134 (2014). https://doi.org/10.1007/s00108-013-3305-9

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