Hier finden Sie wissenschaftliche Publikationen aus den Fraunhofer-Instituten.

Validation of a distinct psoriatic arthritis risk variant at IL23R

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


Rheumatology 55 (2016), Supplement 1, Abstract 219, S.i150-i151
ISSN: 1462-0324
ISSN: 1462-0332
British Society for Rheumatology, British Health Professionals in Rheumatology and the British Society for Paediatric and Adolescent Rheumatology (Annual Meeting Rheumatology) <2016, Glasgow>
Fraunhofer IME ()

Background: PsA is an inflammatory arthritis that is associated with psoriasis and is estimated to present in ∼14% of psoriasis patients in the UK. 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 a risk for psoriasis. We have recently reported evidence of specific loci that confer a risk for PsA and not psoriasis, including a variant at IL23R that was also found to be independent of a 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 < 1.0 × 10−4). 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. Genotype data were also available from the psoriasis WTCCC2 study (excluding known PsA, n = 1784). Multinomial logistic regression was carried out in Stata to compare effect estimates in PsA and psoriasis using PsA Immunochip data (n = 1962). A direct comparison of PsA and psoriasis genotypes was also performed.
Results: We found a significant association for the SNP rs12044149 mapping to IL23R (P = 4.03 × 10−6). A weak association was found with the psoriasis risk variant rs9988642, which has been reported at the same locus (P = 0.04). The association with rs12044149 remained significant when conditioning upon rs9988642 (Pcond = 4.86 × 10−6). Likewise, rs9988642 remained significantly associated with psoriasis when conditioning upon rs12044149 (P = 1.0 × 10−7 vs Pcond 1.63 × 10−5), indicating that they represent independent effects. Effect estimates for rs12044149 were significantly different between PsA and psoriasis (P = 2.0 × 10−3). When genotypes for rs12044149 were directly compared between PsA and psoriasis, the risk allele was significantly increased in PsA (P = 1.91 × 10−3, odds ratio = 1.2).
Conclusion: For the first time we have been able to successfully validate a PsA-specific (associated with PsA but not psoriasis) risk variant at the IL23R locus in an independent cohort, confirming rs12044149 to be independent of rs9988642 (r2 = 0.01). This now gives a total of four PsA-specific associations that have been identified. Such variants could potentially provide markers to identify psoriasis patients who are prone to developing PsA. IL-23 is a target for the psoriasis drug ustekinumab, which has also shown efficacy in PsA during clinical trials. Therefore it would be interesting to explore the role of disease-specific risk variants in treatment response.
Disclosure statement: The authors have declared no conflicts of interest.