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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis.
Nat. Genet. 42, 996-999 (2010)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
GENETIC ASSOCIATION; DISEASE; IL23R; IL12B; ACT1
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Journal
Nature Genetics
Quellenangaben
Volume: 42,
Issue: 11,
Pages: 996-999
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)