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.
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
Ulrike
U
Hüffmeier
Steffen
S
Uebe
Arif B
AB
Ekici
John
J
Bowes
Emiliano
E
Giardina
Eleanor
E
Korendowych
Kristina
K
Juneblad
Maria
M
Apel
Ross
R
McManus
Pauline
P
Ho
Ian N
IN
Bruce
Anthony W
AW
Ryan
Frank
F
Behrens
Jesús
J
Lascorz
Beate
B
Böhm
Heiko
H
Traupe
Jörg
J
Lohmann
Christian
C
Gieger
Heinz-Erich
HE
Wichmann
Christine
C
Herold
Michael
M
Steffens
Lars
L
Klareskog
Thomas F
TF
Wienker
Oliver
O
Fitzgerald
Gerd-Marie
GM
Alenius
Neil J
NJ
McHugh
Giuseppe
G
Novelli
Harald
H
Burkhardt
Anne
A
Barton
André
A
Reis
D048868:Adaptor Proteins, Signal Transducing; D015535:Arthritis, Psoriatic / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004261:DNA Replication; D004200:Diseases in Twins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007378:Interleukins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*; D014430:Twins, Monozygotic
D048868:Adaptor Proteins, Signal Transducing; D007378:Interleukins; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins