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Objective To identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) compared with healthy individuals. Methods RNA was extracted from PBMCs collected from 18 patients with active disease and 18 gender-matched and age-matched controls. Expression profiles of these cells were determined using microarray. Candidate genes with differential expressions were confirmed in the same samples using quantitative reverse transcription-PCR (qRT-PCR). These genes were then validated in a different sample cohort of 35 patients with AS and 18 controls by qRT-PCR. Results Microarray analysis identified 452 genes detected with 485 probes which were differentially expressed between patients with AS and controls. Underexpression of NR4A2, tumour necrosis factor AIP3 (TNFAIP3) and CD69 was confirmed. These genes were further validated in a different sample group in which the patients with AS had a wider range of disease activity. Predictive algorithms were also developed from the expression data using receiver-operating characteristic curves, which demonstrated that the three candidate genes have ~80% power to predict AS according to their expression levels. Conclusions The findings show differences in global gene expression patterns between patients with AS and controls, suggesting an immunosuppressive phenotype in the patients. Furthermore, downregulated expression of three immune-related genes was confirmed. These candidate genes were also shown to be strong predictive markers for AS.

Background Ankylosing spondylitis is a common chronic immune-mediated arthropathy affecting primarily joints of the spine and pelvis. The condition is strongly associated with HLA-B27, and association with other HLA variants has been demonstrated. In addition to these effects, to date 30 non-MHC loci have been associated with the disease, and significant additional heritability remains. Objectives To identify further genetic variants associated with ankylosing spondylitis. Methods We undertook a study of ankylosing spondylitis using 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. This assays all coding variation in the genome along with genomewide association hits and major histocompatibility tag single nucleotide polymorphisms. Analysis was carried out with logistic regression using principal component analysis to correct for any population stratification. Results Novel associations achieving genomewide significance were found in USP8 ( P =3.5 x 10 -52 , OR =1.97) and CDKAL1 ( P =1.8 x10 -8 , OR =1.18). Suggestive associations with common variants in FAM118A ( P =5.9 x 10 -8 , OR =1.16), C7orf72 ( P =1.9 x 10 -7 , OR =1.14) and FAM114A1 ( P =1.4 x 10 -6 , OR =1.14) were also found. A low frequency association (MAF cases/controls: 0.0044/0.0017) was found in patatin-like phospholipase domain containing 1 ( PNPLA1) at a suggestive level of significance ( P =1.5 x 10 -6 , OR =2.6). Conclusions This study describes novel genetic associations with ankylosing spondylitis. Three of the variants have been previously associated with inflammatory bowel disease, and one variant with low hip bone mineral density. These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having very similar aetiopathogenesis. Disclosure of Interest None declared

Background Gout results from innate immune response to monosodium urate (MSU) crystals that form when serum urate is elevated. Identification of genetic risk factors for hyperuricemia and the MSU immune response is therefore important for insight into the etiology of gout. Whilst genome-wide association studies have provided significant insights into the causes of hyperuricemia there are no confirmed loci for non-serum urate pathways in gout. Recently association of the rs2149356 variant in the TLR4 locus with gout was reported in a Chinese sample set (odds ratio TT genotype =1.88, P =8x10–5)1. TLR4 triggers innate immune response to endogenous ligands, including MSU crystals2. Objectives To test rs2149356 for association in European and New Zealand (NZ) Polynesian gout case-control sample sets. Methods All gout cases were clinically ascertained according to the American Rheumatism Association criteria. European cases (n=1606) were recruited from New Zealand (n=599), by the Eurogout consortium within the European Crystal Network (n=784) and by the Arthritis Genomics Recruitment Initiative in Australasia (AGRIA; n=223). European non-gouty controls (n=8066) were recruited from NZ (n=875) and sourced from the Atherosclerosis Risk in Communities (n=4144) and Framingham Heart (n=3047) studies. There were 872 New Zealand Maori and Pacific Island (Polynesian) cases and 1088 controls. Genotyping was done by Taqman and statistical analysis by STATA. Results Using unstratified controls the T allele, but not the TT genotype, was associated with gout in Europeans (ORTallele=1.09, P =0.05; ORTTgenotype=1.15, P =0.13). There was no evidence for association in Polynesians (ORTallele=0.90, P =0.12; ORTTgenotype=0.88, P =0.31). However, comparison of cases to hyperuricemic controls strengthened evidence for association with gout in Europeans (ORTallele=1.18, P =0.004; ORTTgenotype=1.38, P =0.017), but made no difference in Polynesians (ORTallele=, P =0.30; ORTTgenotype=0.87, P =0.47). ![Figure][1] Conclusions The previous report of association of TLR4 with gout in Chinese was replicated in Europeans but not Polynesians. Strengthening of association using hyperuricemic controls is consistent with a role for this locus in gouty inflammation in the presence of hyperuricemia. Subject to further replication, TLR4 represents the first non-serum urate genetic risk locus identified in gout, and provides support for a role of TLR4 in etiology. References 1. Qing et al. PLoS One 2013;5:e64845. 2. Liu-Bryan et al. Arthritis Rheum 2005;52:2936 Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4781 [1]: pending:yes