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

Nat Genet. 2010 Nov;42(11):996-9. doi: 10.1038/ng.688. Epub 2010 Oct 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Arthritis, Psoriatic / genetics*
  • Chromosomes, Human, Pair 6 / genetics*
  • DNA Replication
  • Diseases in Twins / genetics
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Interleukins / genetics
  • Polymorphism, Single Nucleotide*
  • Psoriasis / genetics*
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics*
  • Twins, Monozygotic

Substances

  • Adaptor Proteins, Signal Transducing
  • Interleukins
  • TRAF3IP2 protein, human
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins