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

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

Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis

“…The GWAS for PsA has been described before (3). Briefly, for association at the genome-wide level, allele frequencies of 1,585,307 SNPs were compared between 572 PsA patients and 888 control probands (the Cooperative Health Research in the Region of Augsburg research platform).…”

“…The case-control cohorts used for validation studies were also very similar to the ones described previously (3). As in the previous study, German, Italian, and Swedish patients as well as German control individuals were genotyped in Erlangen using TaqMan Open Array Genotyping Plates (as part of one 32-Plex Panel) or single TaqMan SNP genotyping assays produced by Life Technologies.…”

“…As in the previous study, German, Italian, and Swedish patients as well as German control individuals were genotyped in Erlangen using TaqMan Open Array Genotyping Plates (as part of one 32-Plex Panel) or single TaqMan SNP genotyping assays produced by Life Technologies. The frequency distribution of SNP alleles in Swedish patients was compared to a populationbased control study taken from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study as described previously (3 Twenty-one of 22 selected SNPs were successfully genotyped (Ն95% genotyping rate) ( Tables 1 and 2) and fulfilled Hardy-Weinberg equilibrium in the German, Italian, and Swedish patients and German and Italian controls. Except for rs10772316, SNP genotypes of British individuals were available either from the genome-wide data set or from successful individual genotyping (6 SNPs).…”

HLA-C, CSTA and DS12346 susceptibility alleles confer over 100-fold increased risk of developing psoriasis: evidence of gene interaction

“…Although there seems to be a redundancy in genes with a role in epidermal barrier function contributing to disease susceptibility, recent studies highlight also the synergistic role of the immune system in disease pathogenesis by identifying several new susceptibility loci for psoriasis [18][19][20][21] and suggesting a close interaction between epidermal barrier impairment and both innate and adaptive immune system dysfunction for disease development. 22 In the present study, data analysis point towards a very close interaction between the three susceptibility loci PSORS1, PSORS4 and PSORS5, suggesting a striking 105-fold risk for an HLA-Cw6 +ve individual who carries two copies of the risk allele at both the CSTA and D1S2346 loci.…”

A new approach to combined therapy of psoriasis

“…В проявлении патологии задействова-ны большие группы взаимодействующих генов с измененной экспрессией [4][5][6], изменение опреде-ленных участков хромосом (CNVs), локусы, ассоци-ированные с псориазом [7][8][9]. Однако запуск пато-логического процесса осуществляется не только со-вокупным эффектом перечисленных генетических факторов, но и внешними триггерами и эпигенети-ческими механизмами.…”