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Validation of a distinct psoriatic arthritis risk variant at IL23R

: Budu-Aggrey, A.; Bowes, J.; Lohr, S.; Zervou, M.I.; Helliwell, P.S.; Ryan, A.W.; Kane, D.; Korendowych, E.; Giardina, E.; Packham, J.; McManus, R.; FitzGerald, O.; McHugh, N.J.; Behrens, F.; Burkhardt, H.; Huffmeier, U.; Martin, J.; Goulielmos, G.; Ho, P.; Reis, A.; Barton, A.

Arthritis & rheumatology 67 (2015), Supplement S10, Abstract 100
ISSN: 2326-5191
ISSN: 2326-5205
American College of Rheumatology/Association of Reproductive Health Professionals (ACR/ARHP Annual Meeting) <2015, San Francisco/Calif.>
Fraunhofer IME ()

Background/Purpose: Psoriatic Arthritis (PsA) is an inflammatory arthritis that is associated with psoriasis. In the UK, it is estimated to present in approximately 14% of psoriasis patients. PsA is a complex disease that is influenced by both genetic and environmental factors. Genetic studies have aided the discovery of PsA risk loci, the majority of which also confer risk for psoriasis. We have recently reported evidence of specific loci that confer risk for PsA and not psoriasis, including a variant at IL23R which was also found to be independent of the psoriasis variant reported at the same locus.
Methods: In this study, we attempted to identify additional PsA-specific risk variants by genotyping 32 single nucleotide polymorphisms (SNPs) which included those found to have nominal significance in our recent Immunochip study (P <1x10-4) as well as SNPs selected from other studies. These were analysed in 914 PsA cases and 6945 controls from the UK, Crete, Spain and Germany which were independent from those genotyped as part of the Immunochip study. Genotyping was performed using the Life Technologies QuantStudio genotyping platform and association testing was carried out using PLINK. SNPs and samples with poor call rates (<0.9) were excluded prior to analysis.
Results: We found a significant association for the SNP rs12044149 mapping to IL23R (P = 4.03x10-6). A very weak association was found with the psoriasis variant rs9988642, which has been reported at the same locus (P = 0.04). This supports the evidence previously reported of rs12044149 being distinct from rs9988642 and associated with PsA, as demonstrated by the conditional analysis carried out in our Immunochip study [1].
For the first time we have been able to successfully validate a PsA-specific risk variant at the IL23R locus in an independent cohort. This now gives us a total of four PsA-specific associations that have been identified. Such variants could potentially provide us with a marker to identify psoriasis patients who are prone to developing PsA. IL23 is a target for the psoriasis drug ustekinumab which has also shown efficacy in PsA during clinical trials. It would be interesting to explore whether disease-specific risk variants identifies those PsA patients likely to respond to the drug.