PSORS13 (Psoriasis Susceptibility 13) is a genetic locus associated with psoriasis. PSOS13 is located on chromosome 6q21.
This psoriasis susceptibility locus (PSORS13) has been shown to be conferred by variations in the TRAF3IP2 gene (607043) on chromosome 6q21.
Ellinghaus et al (2010) performed a genome-wide association analysis of over 2 million single nucleotide polymorphisms (SNPs) in 472 psoriasis vulgaris cases and 1 146 controls from Germany, tracing the 147 most significant SNPs in 2 746 psoriasis vulgaris cases and 4 140 controls from three independent replication panels. The authors identified an association at TRAF3IP2 on 6q21 and genotyped 2 SNPs at this locus. Approximately 15% of psoriasis cases develop psoriatic arthritis. Stratified analysis of their datasets, which included only psoriatic arthritis cases (1 922 cases versus 8 037 controls, P = 4.57 x 10(-12) for rs33980500), suggested that TRAF3IP2 represents a common susceptibility to psoriasis vulgaris and psoriatic arthritis. TRAF3IP2 encodes a protein involved in interleukin-17 signaling that interacts with members of the Rel/NF-kappa-B transcription factor family. An association with HLA-Cw6 was not detectable.
Huffmeier et al (2010) performed a genome-wide association study in 609 German individuals with psoriatic arthritis and 990 controls, which was replicated in 6 European cohorts totaling 5,488 individuals. The authors replicated associations with psoriatic arthritis in HLA-C (177900) and IL12B (612599). Furthermore, they identified a novel association in TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with psoriasis vulgaris in a German cohort of 2 040 individuals. Sequencing of the exons of TRAF3IP2 identified a coding variant, rs33980500, (asp10 to asn) as the most strongly associated SNP (P = 1.13 x 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6 (602355), suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a novel and common pathway for psoriatic arthritis and psoriasis vulgaris.