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Nature Research, Nature Genetics, 11(42), p. 996-999, 2010

DOI: 10.1038/ng.688

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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

Journal article published in 2010 by Ulrike Hüffmeier, Steffen Uebe, Arif B. Ekici, John Bowes, Emiliano Giardina, Eleanor Korendowych, Kristina Juneblad, Maria Apel, Ross McManus, Pauline Ho, Ian N. Bruce, Anthony W. Ryan, Frank Behrens, Jesús Lascorz, B. Bohm and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.