Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Association of ERAP1, IL12B and IL23R Gene Polymorphisms with Subphenotypes of Psoriatic Arthritis.
Jadon1, Deepak, Tillett1, William, Wallis1, Dinny, Cavill2, Charlotte, Dixon2, Anna, Waldron1, Nicola, Korendowych1, Eleanor
Genetic studies have demonstrated an association between interleukin-23 receptor (IL23R) and interleukin-12 beta (IL12B) gene variants and susceptibility to psoriatic arthritis (PsA)1,2, ankylosing spondylitis (AS)3 and psoriasis4. Endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants have shown association with AS5 and psoriasis6.
We now investigate whether single-nucleotide polymorphisms (SNPs) in the genes encoding ERAP1, IL23R and IL12B associate with specific clinical phenotypes within PsA, such as those with spinal involvement of PsA.
262 PsA patients (131 males, median age at PsA onset 38 years) living in South-West England were compared with healthy controls derived from the Wellcome Trust Case Control Consortium; 3266 controls for ERAP1 (rs30187), 5422 for IL12B (rs6887695) and 4941 for IL23R (rs11209026 and rs7530511) genes.
These SNPs were genotyped in PsA cases and controls using the Sequenom MassARRAY platform.
98.5% of cases fulfilled the CASPAR classification for PsA. The following clinical phenotypes were assessed; age at onset of psoriasis/PsA, number of arthritic joints, axial radiographic disease (defined as spondylitis/sacroiliitis or both), peripheral radiographic erosions, Psoriasis Area Severity Index, nail score and HAQ.
Statistical analysis was performed using the Pearson Chi-Square test or the Mann-Whitney-U test as appropriate.
Genotype frequencies in cases and controls were in Hardy-Weinberg equilibrium.
There was a strong association between rs6887595 (IL12B) and PsA, with homozygosity for the major allele being more frequent in PsA than controls (odds ratio 1.7; 95% confidence interval 1.32.2; p<0.001).
A trend was demonstrated for the minor allele of rs11209026 to be less frequent in patients with erosive joint disease than in those without erosion or controls (6.9%, 13.3% and 12.8%, respectively).
None of the four SNPs associated with the presence of radiological axial disease or other clinical subphenotypes.
We have confirmed a strong association between rs6887595 (IL12B gene) and PsA. A trend has been demonstrated between an IL23R variant and peripheral erosive disease. Contrary to our hypothesis, no association was demonstrated between these known AS-associated SNPs and the presence of radiological axial disease, non-polyarticular or non-erosive disease that would suggest a PsA subphenotype towards the AS spectrum. ERAP1 encodes a pair of trimming aminopeptidases located in the endoplasmic reticulum, that have complementary functions in human leucocyte antigen (HLA) class 1 peptide presentation. Therefore ERAP1 in particular may exert an effect dependent on HLA-B27 and HLA-Cw6 status, as was demonstrated in a study of psoriasis6. We will now explore this with a larger sample size.
To cite this abstract, please use the following information:
Jadon, Deepak, Tillett, William, Wallis, Dinny, Cavill, Charlotte, Dixon, Anna, Waldron, Nicola, et al; Association of ERAP1, IL12B and IL23R Gene Polymorphisms with Subphenotypes of Psoriatic Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1366