CoMon variants at TRAF3IP2 are aSociated with susceptibility to psoriatic arthritis and psoriasis

Abstract

Psoriatic arthritis (PsA) is an inflaMatory joint disease that is distinct from other chronic arthritides and which is frequently aCompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide aSociation 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 aSociations at HLA-C and IL12B and identified a new aSociation at TRAF3IP2 (rs13190932, P = 8.56-10-17). TRAF3IP2 was also aSociated 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 aSociated SNP (P = 1.13-10-20, oDs ratio = 1.95). Functional aSays showed reduced binding of this TRAF3IP2 variant to TRAF6, suGesting altered modulation of iMunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV. © 2010 Nature America, Inc. All rights reserved.