SAT0460 Association between inflammasome-related polymorphisms and psoriatic arthritis
Authors: K Juneblad, A Kastbom, S Rantapää-Dahlqvist, P Söderkvist, G-M Alenius
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In recent years, research on the interleukin 1β(IL1 β)–regulating protein complex, called the inflammasome, has shown interesting associations with various inflammatory diseases. E.g. for Rheumatoid Arthritis (RA) (1) and psoriasis (Pso) (2, 3) associations with genetic polymorphisms in genes related to the inflammasome has been discovered. So far, no studies investigating genetic polymorphisms in inflammasome genes in Psoriatic Arthritis (PsA) patients have been published. <h3>Objectives</h3> To examine whether polymorphisms in genes related to inflammasomes confer increased risk for psoriatic arthritis. <h3>Methods</h3> DNA from 771 PsA patients and 793 healthy controls from Sweden were analyzed for different single nucleotide polymorphisms (SNPs) in <i>NLRP3</i> (rs35829419, rs10733113, rs4353135), <i>CARD8</i> (rs 2043211) and <i>NLRP1</i> (rs8079034, rs878329). <h3>Results</h3> Significant associations with PsA were found between carriage of allele, C, of rs878329 in <i>NLRP1</i> (Chi-2=6.5, OR (95% CI); 0.75 (0.60–0.94), P=0.011) and allele G in rs4353135 in <i>NLRP3</i> (Chi-2=4.8, OR (95% CI); 1.25 (1.02–1.53), p=0.028). Genotype distribution were also significantly different between patients and controls and for rs878329 in <i>NLRP1</i> there was a significant difference in allele frequency (G/C) between patients and controls (Chi-2=5.8, OR (95% CI); 1.20 (1.03–1.38), p=0.016). No significant associations with PsA were found for the other SNPs analyzed. In genotype analysis, a significant higher frequency of genotype GG in rs878329 in PsA was detected (32.9% vs 26.9%, Chi-2=6.49, OR (95% CI); 1.34 (1.07–1.67), p=0.011), whilst no significant differences were detected for genotypes GC or CC. For rs4353135, a significantly higher frequency of genotype TG (43% vs 37.6%, Chi-2=4.66, OR (95% CI); 1.25 (1.02–1.53), P=0.033) and a significantly lower frequency of genotype TT (50.5% vs 56.1%, Chi-2=4.85, OR (95% CI); 0.80 (0.65–0.98), P=0.028) was seen in PsA, no significan difference was detected for genotype GG. <h3>Conclusions</h3> Carriage of rs878329C in <i>NLRP1</i> was less frequent in patients with PsA compared with controls indicating a protecting effect, but when different genotypes were analysed the difference likely results from an increased risk of PsA with genotype GG. The results are in contrast with the study of Ekman <i>et al</i>, where an increased transmission of rs878329C to family members with psoriasis was seen (3), indicating an increased risk of developing skin psoriasis for carriers of C, but in agreement with the study of Sui <i>et al</i> on patients with RA, where an association was detected for carriage of C (OR 0.82, p=0.02), with the risk genotype for RA being GG (4). Thus, the genotype GG possibly confers risk of arthritic disease whilst the C-allele seems associated with skin disease. Carriage of rs4353135G in <i>NLRP3</i> was more frequent in PsA patients compared with controls indicating an increased risk of disease, but only genotype GT was significantly increased in PsA. The study is, to our knowledge, the first to study possible associations between genes related to the inflammasome and PsA. In the study associations were found between one SNP in <i>NLRP3</i> and one SNP in <i>NLRP1</i>, indicating a possible involvement in pathogenesis of PsA disease. <h3>References</h3> Rheumatol 2008;47:415–7. Exp Dermatol 2012;21:932–7. Br J Rheumatol 2014;171:1517–20. Arthritis Rheum 2012;64:647–54. <h3>Disclosure of Interest</h3> None declared