TY  - JOUR
A1  - Böhm, Beate B.
A1  - Burkhardt, Harald
A1  - Uebe, Steffen
A1  - Apel, Maria
A1  - Behrens, Frank
A1  - Reis, André
A1  - Hüffmeier, Ulrike
T1  - Identification of low-frequency TRAF3IP2 coding variants in psoriatic arthritis patients and functional characterization
T2  - Arthritis Research & Therapy
N2  - 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.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24838
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-248387
SN  - 1465-9913
SN  - 1478-6362
SN  - 1478-6354
VL  - 14
IS  - R84
PB  - BioMed Central
CY  - London
ER  -