FRI0420 Association of supressor of cytokine signaling -3 (SOCS-3) expression with interleukin-23 receptor (IL-23R) single nucleotide polymorphisms (SNPS) in ankylosing spondylitis (AS)
Authors: MA Sánchez, R Villares, J Polo y La Borda, J Campos, JM Rodríguez-Frade, J Sanz, BJ Robles Flores, A Royuela, P Lucas, M Mellado, J Mulero
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Nowadays genetic-association studies have discovered new genes, other than <i>HLA-B27</i>, as <i>IL-23R</i> associated with AS. The signalling pathway trough IL-23R is negatively regulated by the SOCS proteins. However, the reports regarding the roles of SOCS in AS are very rare at present.<sup>1,2</sup> <h3>Objectives</h3> The aim of this study is to assess the gene expression of <i>SOCS-1</i>, <i>-2,</i><i>-3</i>and <i>-6</i> in peripheral blood mononuclear cells (PBMCs) in relation with <i>IL-23R</i> SNPs previously associated with AS. <h3>Methods</h3> We studied 74 patients (64,8% males) recruited from the Rheumatology Unit of the Puerta de Hierro Hospital diagnosed of AS following the Modified New York Criteria. The study cohort included patients with a mean age of 55.2±11, 2 years. Total RNA was extracted from PBMCs using the Nucleospin RNA kit (MN) and reverse transcribed into cDNA. mRNA expression was assessed by real-time quantitative RT-PCR using specific primers and Power SYBRGreen PCR Master Mix (Applied Biosystems).SNP genotyping [rs1129026 (G/A), rs10489629 (T/C), rs1343151 (G/A) rs2201841 (C/T), rs1004819 (C/T) y rs11209032 (A/G)] was performed using the Sequenom MassARRAY platform. In 17 cases there were two samples from the same patient. These samples were obtained from two scheduled visits and 99 samples were analyzed so. To determine the effect of independent variables on levels of <i>SOCS</i> genes expression, we fitted population-averaged models by generalized linear models, nested by patient, using the <i>xtgee</i> command of Stata v.12. <i>P</i>-values of &lt;0.05 were considered statistically significant. <h3>Results</h3> Cellular <i>SOCS-1</i>,<i>-2</i> and <i>-6</i> expression did not show significant differences between the risk alleles carriers and the protective alleles carriers in any of the <i>IL-23R</i> SNP studied. <i>SOCS-3</i> increased significantly in protective alleles carriers of the <i>IL-23R</i> intronic SNP rs10489629-C (CC&gt;CT&gt;TT; <i>P</i>=0.028), the <i>IL-23R</i> non-synonymous SNP (Arg381Gln) rs11209026_A (AG&gt;GG; <i>P</i>=0.047) and the <i>IL-23R</i> intronic SNP rs1343151-A (AA&gt;AG&gt;GG, <i>P</i>=0.005). <h3>Conclusions</h3> Higher <i>SOCS-3</i> expression levels for AS patients carriers of protective alleles of the <i>IL-23R</i> rs10489629-A, rs11209026-A and rs1343151-A as compared to carriers of risk genotypes could influence the pathogenesis of this disease. <h3>References</h3> Mol Biol Rep. 2014;41(6):3773–80. Clin Exp Rheumatol. 2016;34(1):100–5. <h3>Acknowledgements</h3> This work have been supported by Fondo de Investigaciones Sanitarias (PI11/00400) and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+I 2008–2011, (FEDER). <h3>Disclosure of Interest</h3> None declared