title: Variants in RUNX3 contribute to susceptibility to psoriatic arthritis, exhibiting further common ground with ankylosing spondylitis.
abstract: OBJECTIVE
  Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis.
  
  
  METHODS
  Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris.
  
  
  RESULTS
  Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 × 10(-8) by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.15-1.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 × 10(-2) ; OR 1.13 [95% CI 1.00-1.28]), indicating a role in the skin manifestations of psoriasis.
  
  
  CONCLUSIONS
  Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cell-mediated diseases.
authors: University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Maria
authors: M
authors: Apel
authors: Steffen
authors: S
authors: Uebe
authors: John
authors: J
authors: Bowes
authors: Emiliano
authors: E
authors: Giardina
authors: Eleanor
authors: E
authors: Korendowych
authors: Kristina
authors: K
authors: Juneblad
authors: Francesca
authors: F
authors: Pasutto
authors: Arif B
authors: AB
authors: Ekici
authors: Ross
authors: R
authors: McManus
authors: Pauline
authors: P
authors: Ho
authors: Ian N
authors: IN
authors: Bruce
authors: Anthony W
authors: AW
authors: Ryan
authors: Frank
authors: F
authors: Behrens
authors: Beate
authors: B
authors: Böhm
authors: Heiko
authors: H
authors: Traupe
authors: Jörg
authors: J
authors: Lohmann
authors: Christian
authors: C
authors: Gieger
authors: Heinz-Erich
authors: HE
authors: Wichmann
authors: Leonid
authors: L
authors: Padyukov
authors: Oliver
authors: O
authors: Fitzgerald
authors: Gerd-Marie
authors: GM
authors: Alenius
authors: Neil J
authors: NJ
authors: McHugh
authors: Giuseppe
authors: G
authors: Novelli
authors: Harald
authors: H
authors: Burkhardt
authors: Anne
authors: A
authors: Barton
authors: André
authors: A
authors: Reis
authors: Ulrike
authors: U
authors: Hüffmeier
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human