Variants in RUNX3 contribute to susceptibility to psoriatic arthritis exhibiting further common ground with ankylosing spondylitis

Maria Apel, Steffen Uebe, John Bowes, Emiliano Giardina, Eleanor Korendowych, Kristina Juneblad, Francesca Pasutto, Arif B Ekici, Ross McManus, Pauline Ho, Ian N Bruce, Anthony W Ryan, Frank Behrens, Beate Böhm, Heiko Traupe, Jörg Lohmann, Christian Gieger, Heinz-Erich Wichmann, Leonid Padyukov, Oliver FitzgeraldGerd-Marie Alenius, Neil J McHugh, Giuseppe Novelli, Harald Burkhardt, Anne Barton, André Reis, Ulrike Hüffmeier

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

OBJECTIVE: Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris (PsV). 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 is not fully explained. Therefore we investigated further 17 loci from our GWAS which did not reach genome-wide significance levels of association in the initial analysis.

METHODS: 21 of 22 single nucleotide polymorphisms (SNPs) were successfully genotyped in independent cohorts of 1,398 PsA cases and 6,389 controls, and a group of 964 German PsV patients.

RESULTS: Association to a RUNX3 variant, rs4649038, was replicated in independent cases and controls and resulted in a combined p-value of 1.40E-08 in a Cochran-Mantel-Haenszel test and an OR of 1.24 (1.15-1.33). Further analyses based on linkage disequilibrium at RUNX3 refined the most significant association to a linkage disequilibrium (LD) block located in the first intron of one isoform. Weaker evidence for association was detected in German PsV patients (p-value 5.89E-02; OR 1.13 (1.00-1.28)), indicating a role in the skin manifestations of psoriasis.

CONCLUSION: Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondylarthropathy, although its risk allele is independent from the PsA one. RUNX3 is involved in CD8 lymphocyte differentiation and therefore a good candidate for PsA and PsV as T-cell mediated diseases.
Original languageEnglish
Pages (from-to)1224-1231
JournalArthritis & Rheumatism
Volume65
Issue number5
Early online date22 Apr 2013
DOIs
Publication statusPublished - May 2013

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