Psoriasis 13, Susceptibility To

<p>A number sign (#) is used with this entry because of evidence that susceptibility to psoriasis (PSORS13) is conferred by variation in the TRAF3IP2 gene (607043) on chromosome 6q21.p><p>For a phenotypic description and a discussion of genetic heterogeneity of psoriasis, see PSORS1 (177900).p> Mapping <p>Ellinghaus et al. (2010) performed a genomewide association analysis of over 2 million single-nucleotide polymorphisms (SNPs) in 472 psoriasis vulgaris cases and 1,146 controls from Germany, with follow-up of the 147 most significant SNPs in 2,746 psoriasis vulgaris cases and 4,140 controls from 3 independent replication panels. Ellinghaus et al. (2010) identified an association at TRAF3IP2 on 6q21 and genotyped 2 SNPs at this locus in 2 additional replication panels (the combined discovery and replication panels consisted of 6,487 cases and 8,037 controls; combined P = 2.36 x 10(-10) for rs13210247 and combined P = 1.24 x 10(-16) for rs33980500). About 15% of psoriasis cases develop psoriatic arthritis. A stratified analysis of their datasets including only psoriatic arthritis cases (1,922 cases compared to 8,037 controls, P = 4.57 x 10(-12) for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for psoriasis vulgaris and psoriatic arthritis. TRAF3IP2 encodes a protein involved in IL17 (603149) signaling and interacts with members of the Rel/NF-kappa-B transcription factor family (see 164014). Ellinghaus et al. (2010) tested for the presence of statistical interaction between rs33980500 (asp19 to asn) genotypes and HLA-Cw6 (see 142840.0001) carriership in a subset of 993 cases and 2,277 controls for whom HLA-Cw6 status was available, and found no statistical support for interaction (P = 0.77). p><p>Huffmeier et al. (2010) conducted a genomewide association study in 609 German individuals with psoriatic arthritis and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. Huffmeier et al. (2010) replicated psoriatic arthritis associations at HLA-C (177900) and IL12B (612599) and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with psoriasis vulgaris in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant, rs33980500, (asp10 to asn) as the most significantly 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 shared pathway for psoriatic arthritis and psoriasis vulgaris. p>