Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
Copyright policy )Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
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.
- University of Rome Tor Vergata Italy
- Trinity College Dublin Ireland
- Karolinska Institute Sweden
- Goethe University Frankfurt Germany
- University of Bath United Kingdom
single nucleotide, DNA Replication, chromosomes, Genotype, genotype, pair 6, diseases in twin, Settore MED/03 - GENETICA MEDICA, Polymorphism, Single Nucleotide, Article, polymorphism, monozygotic, Diseases in Twins, Humans, Psoriasis, Genetic Predisposition to Disease, human, humans, psoriasis; chromosomes, human, pair 6; diseases in twins; twins, monozygotic; polymorphism, single nucleotide; dna replication; tumor necrosis factor receptor-associated peptides and proteins; arthritis, psoriatic; interleukins; genotype; genetic predisposition to disease; humans, psoriasi, Adaptor Proteins, Signal Transducing, genetic predisposition to disease, dna replication, interleukin, Interleukins, tumor necrosis factor receptor-associated peptides and protein, Arthritis, Psoriatic, twins, Twins, Monozygotic, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, arthritis, Chromosomes, Human, Pair 6, psoriatic
single nucleotide, DNA Replication, chromosomes, Genotype, genotype, pair 6, diseases in twin, Settore MED/03 - GENETICA MEDICA, Polymorphism, Single Nucleotide, Article, polymorphism, monozygotic, Diseases in Twins, Humans, Psoriasis, Genetic Predisposition to Disease, human, humans, psoriasis; chromosomes, human, pair 6; diseases in twins; twins, monozygotic; polymorphism, single nucleotide; dna replication; tumor necrosis factor receptor-associated peptides and proteins; arthritis, psoriatic; interleukins; genotype; genetic predisposition to disease; humans, psoriasi, Adaptor Proteins, Signal Transducing, genetic predisposition to disease, dna replication, interleukin, Interleukins, tumor necrosis factor receptor-associated peptides and protein, Arthritis, Psoriatic, twins, Twins, Monozygotic, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, arthritis, Chromosomes, Human, Pair 6, psoriatic
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