Identification of low-frequency TRAF3IP2 coding variants in psoriatic arthritis patients and functional characterization

INTRODUCTION: In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease en
INTRODUCTION: In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease entities. The risk allele of p.Asp10Asn (rs33980500) proved to be most significantly associated and to encode a mutant protein with an almost completely disrupted binding property to TRAF6, supporting its impact as a main disease-causing variant and modulator of IL-17 signaling.
METHODS: To identify further variants, exons 2-4 encoding both known TNF-receptor-associated factor (TRAF) binding domains were sequenced in 871 PsA patients. Seven missense variants and one three-base-pair insertion were identified in 0.06% to 1.02% of alleles. Five of these variants were also present in 931 control individuals at comparable frequency. Constructs containing full-length wild-type or mutant TRAF3IP2 were generated and used to analyze functionally all variants for TRAF6-binding in a mammalian two-hybrid assay.
RESULTS: None of the newly found alleles, though, encoded proteins with different binding properties to TRAF6, or to the cytoplasmic tail of the IL-17-receptor α-chain, suggesting that they do not contribute to susceptibility.
CONCLUSIONS: Thus, the TRAF3IP2-variant p.Asp10Asn is the only susceptibility allele with functional impact on TRAF6 binding, at least in the German population.
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Metadaten
Author:Beate Böhm, Harald Burkhardt, Steffen Uebe, Maria Apel, Frank Behrens, André Reis, Ulrike Hüffmeier
URN:urn:nbn:de:hebis:30:3-248387
DOI:http://dx.doi.org/doi:10.1186/ar3807
ISSN:1465-9913
ISSN:1478-6362
ISSN:1478-6354
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22513239
Parent Title (English):Arthritis Research & Therapy
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2012/04/18
Date of first Publication:2012/04/18
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/05/22
Volume:14
Issue:Issue 2 ; R84
Pagenumber:5
First Page:1
Last Page:5
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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