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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
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Journal Article
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
2010
Overview
André Reis and colleagues report a genome-wide association study identifying a susceptibility locus at
TRAF3IP2
for 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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Adaptor Proteins, Signal Transducing
/ Animal Genetics and Genomics
/ Arthritis, Psoriatic - genetics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Chromosomes, Human, Pair 6 - genetics
/ Diseases in Twins - genetics
/ Diseases of the osteoarticular system
/ Fundamental and applied biological sciences. Psychology
/ Genetic Predisposition to Disease
/ Genetics
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genotype
/ Humans
/ letter
/ Polymorphism, Single Nucleotide
/ Psoriasis. Parapsoriasis. Lichen
/ Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - genetics
