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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?¹?). 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?²?, 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.

SUBMITTER: Huffmeier U

PROVIDER: S-EPMC2981079 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Hüffmeier Ulrike U Uebe Steffen S Ekici Arif B AB Bowes John J Giardina Emiliano E Korendowych Eleanor E Juneblad Kristina K Apel Maria M McManus Ross R Ho Pauline P Bruce Ian N IN Ryan Anthony W AW Behrens Frank F Lascorz Jesús J Böhm Beate B Traupe Heiko H Lohmann Jörg J Gieger Christian C Wichmann Heinz-Erich HE Herold Christine C Steffens Michael M Klareskog Lars L Wienker Thomas F TF Fitzgerald Oliver O Alenius Gerd-Marie GM McHugh Neil J NJ Novelli Giuseppe G Burkhardt Harald H Barton Anne A Reis André A

Nature genetics 20101017 11

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 (rs13190 ...[more]

PMID: 20953186

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Project description:IntroductionPsoriatic arthritis (PsA) is a chronic, inflammatory arthritis that affects an estimated 30% of patients with psoriasis. PsA is underdiagnosed in primary care and dermatology clinics due to a variety of reasons, including failure of healthcare providers to ask about symptoms, overlap of symptoms and signs with other rheumatologic conditions, and lack of a specific diagnostic test. A delay in PsA diagnosis and treatment, even as short as 6 months, can lead to decreased quality of life, increased joint damage, and worse long-term physical function. In this study, we sought to identify the clinical and genetic factors that help discriminate patients with PsA from those with cutaneous psoriasis only.MethodsWe analyzed a cohort of 974 psoriasis patients at an academic medical center, of whom 175 had confirmed PsA, and performed univariate, multivariate, and predictive modeling to determine factors associated with PsA.ResultsThe univariate analysis revealed significant positive associations of PsA with age, nail involvement, scalp involvement, skin fold involvement, elbow/knee involvement, psoriasis severity, plaque subtype, erythrodermic subtype, hypertension, type 2 diabetes, and coronary artery disease, and a significant negative association of PsA with the human leukocyte antigen (HLA)-C*06:02 allele. In the multivariate analysis, nail involvement, type 2 diabetes, and pustular psoriasis remained significantly associated with PsA, while HLA-C*06:02 positivity remained protective. There was a trend towards an association of PsA with older age, younger age of psoriasis onset, and skin fold involvement, while there was protective trend for smoking. A predictive model including both clinical and genetic factors showed reasonable discriminative ability between psoriasis and PsA, with an area under the curve of 0.87 for a receiver operating characteristic curve.ConclusionThis study identified a number of clinical and genetic features that could help stratify patients who are at higher risk for having PsA and for whom rheumatology referral may be beneficial.

Dataset Information

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

Publications

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

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