ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 100

Validation of a Distinct Psoriatic Arthritis Risk Variant at IL23R

Ashley Budu-Aggrey1,2, John Bowes1, Sabine Lohr3, Maria I. Zervou4, Philip S. Helliwell5, Anthony W. Ryan6, David Kane7, Eleanor Korendowych8, Emiliano Giardina9, Jonathon Packham10, Ross McManus6, Oliver FitzGerald11, Neil J McHugh8, Frank Behrens12, Harald Burkhardt12, Ulrike Huffmeier3, Javier Martín13, George Goulielmos4, Pauline Ho1,14, Andre Reis3 and Anne Barton1,2,14, 1Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester, United Kingdom, 2NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester, United Kingdom, 3Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany, 4Laboratory of Molecular Medicine and Human Genetics, Department of Internal Medicine, University of Crete, Heraklion, Greece, 5NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom, 6Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland, 7Adelaide and Meath Hospital and Trinity College Dublin, Dublin, United Kingdom, 8Royal National Hospital for Rheumatic Diseases and Dept Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom, 9Department of Biopathology, Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome 'Tor Vergata' and Fondazione PTV 'Policlinico Tor Vergata', Rome, Italy, 10Rheumatology department, Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University, Staffordshire, United Kingdom, 11Department of Rheumatology, St. Vincent’s University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland, 12Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt, Germany, 13Instituto de Biomedicina y Parasitología López-Neyra, Granada, Spain, 14The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords:

Session Information

Date: Sunday, November 8, 2015

Session Title: Genetics, Genomics and Proteomics Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

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 <1×10-4) 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 = 4.03×10-6). 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].

Conclusion:

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.

References: 1. Bowes J, Budu-Aggrey A, Huffmeier U.et al.  Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nat Commun 2015;6

Disclosure: A. Budu-Aggrey, None; J. Bowes, None; S. Lohr, None; M. I. Zervou, None; P. S. Helliwell, None; A. W. Ryan, None; D. Kane, None; E. Korendowych, None; E. Giardina, None; J. Packham, None; R. McManus, None; O. FitzGerald, None; N. J. McHugh, None; F. Behrens, AbbVie Deutschland GmbH & Co KG; Chugai; Pfizer; Roche, 5,Pfizer Inc, 8; H. Burkhardt, AbbVie Deutschland; Pfizer; BMS; UCB; Chugai, 5,Pfizer Inc, 2; U. Huffmeier, None; J. Martín, None; G. Goulielmos, None; P. Ho, None; A. Reis, None; A. Barton, Eli-Lilly, Pfizer, Abbvie, 2.

To cite this abstract in AMA style:

Budu-Aggrey A, Bowes J, Lohr S, Zervou MI, Helliwell PS, Ryan AW, Kane D, Korendowych E, Giardina E, Packham J, McManus R, FitzGerald O, McHugh NJ, Behrens F, Burkhardt H, Huffmeier U, Martín J, Goulielmos G, Ho P, Reis A, Barton A. Validation of a Distinct Psoriatic Arthritis Risk Variant at IL23R [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/validation-of-a-distinct-psoriatic-arthritis-risk-variant-at-il23r/. Accessed March 1, 2021.

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