Background/Purpose:

A lack of well-characterised clinical cohorts has impeded research of the genetics of axial disease in psoriatic arthritis (PsA). We sought to determine genetic biomarkers of psoriatic spondyloarthritis (PsSpA) occurrence in patients with PsA.

Methods:

A cross-sectional observational study was conducted of all PsA patients attending a teaching hospital. Axial radiographs were examined for the presence of PsSpA, defined as: sacroiliitis grade ≥3 unilaterally, or grade ≥2 bilaterally; and/or ≥1 syndesmophyte of the cervical and/or lumbar spine.

All PsA cases were genotyped using the Illumina Infinium HumanCoreExome Beadchip. In order to determine genetic risk factors for axial disease in PsA, comparisons were made between PsA cases with and without: PsSpA; sacroiliitis; and spondylitis. Multivariate modelling was adjusted for sex, age and disease duration at radiographic assessment. Associated single nucleotide polymorphisms (SNPs) within 100 kb of each other were considered as one locus, and an index SNP identified.

Results:

The study enrolled and genotyped 515 PsA cases fulfilling CASPAR criteria. Of 436/515 with complete radiographs to determine PsSpA, 144/436 (33.03%) had PsSpA and 292/436 (66.97%) did not have PsSpA. Genetic analyses were performed on these 436 cases only.

No single nucleotide polymorphisms (SNPs) passed the conventional genome-wide significance (5×10^-8); a total of seven SNPs were in tier 1 (defined as p-value <1×10^-5). Notable associations include rs11950551 with PsSpA (OR 3.03; 95%CI 1.88, 4.89; p-value 5.42×10^-6) (Table 1) that maps close to gene CD180, belonging to a family of toll-like receptors important in B-cell signalling (Figure 1). Secondly, an insertion on chromosome 4 (rs202217778) within the SMAD1 gene is associated with sacroiliitis (OR 3.98; 95%CI 2.18, 7.27; p-value 7.36×10^-6) but not spondylitis (Table 1, Figure 1). SMAD1has a key role in bone morphogenesis and immune responses.

Forty eight SNPs showing association with psoriasis, PsA or AS in Genome Wide Association Studies, were specifically compared in PsA cases with and without PsSpA. Of note, none of the SNPs were associated with PsSpA.

Conclusion:

We have identified suggestive evidence for association of 24 independent loci associated with axial disease in patients with PsA (PsSpA). The genetic loci associated with sacroiliitis did not overlap either with those associated with vertebral spondylitis in PsA, or with known AS loci. The findings need investigation in validation datasets and the functional influence of confirmed variants on biological pathways may warrant further exploration.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/axial-disease-in-psoriatic-arthritis-genetic-biomarkers-of-psoriatic-spondyloarthritis/