AB0108 Decreased expression of PTPN22 gene in patients with rheumatoid arthritis carrying the risk allele of PTPN22 RS2488457 polymorphism
Authors: S Remuzgo-Martínez, S Castañeda, A Corrales, F Genre, R Lόpez-Mejías, P Moreno-Fresneda, B Ubilla, V Mijares, V Portilla, J González-Vela, T Pina, G Ocejo-Vinyals, J Irure-Ventura, R Blanco, J Martín, J Llorca, MA González-Gay
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Mutations in the protein tyrosine phosphatase non-receptor 22 (<i>PTPN22</i>) gene are associated with numerous connective tissue and autoimmune diseases [1]. In particular, <i>PTPN22</i> has been recognized as the main non-HLA genetic risk factor involved in rheumatoid arthritis (RA) susceptibility [2]. Moreover, it has been suggested that <i>PTPN22</i> modulation may influence on inflammatory processes associated with RA [3,4]. <h3>Objectives</h3> To determine if <i>PTPN22</i> (rs2476601, rs33996649 and rs2488457) polymorphisms, associated with RA, may influence on <i>PTPN22</i> expression in RA patients compared to healthy controls. Moreover, the association between <i>PTPN22</i> expression in patients with RA and their clinical characteristics was studied. <h3>Methods</h3> <i>PTPN22</i> messenger RNA (mRNA) expression was quantified by quantitative real-time PCR in peripheral blood samples from 42 RA patients and 24 healthy controls. <i>PTPN22</i> rs2476601 (G&gt;A), <i>PTPN22</i> rs3399649 (C&gt;T), and <i>PTPN22</i> rs2488457 (C&gt;G) single-nucleotide polymorphisms (SNP) were genotyped by TaqMan SNP genotyping assays. Differences in <i>PTPN22</i> expression between patients and controls were analyzed by Student9s t test, according to their genotype. Correlation coefficients were also assessed between <i>PTPN22</i> expression in RA patients and their clinical characteristics. <h3>Results</h3> A significant down-regulation of <i>PTPN22</i> expression in patients with RA carrying <i>PTPN22</i> rs2488457 risk allele (G) compared to controls was observed (relative mean values of <i>PTPN22</i> mRNA levels ± standard deviation: 2.93±0.76 vs 4.33±0.63, p=0.0004). Furthermore, an inverse relationship between <i>PTPN22</i> expression and disease duration (r=-0.38, p=0.03) was found. These results were adjusted by sex, age at time of study and cardiovascular risk factors. <h3>Conclusions</h3> Our study shows for the first time that the risk allele of <i>PTPN22</i> rs2488457 polymorphism influences on the down-regulation of <i>PTPN22</i> in patients with RA. This result suggests a transcriptional suppression of <i>PTPN22</i> gene in RA, which in turn may play an important role in disease diagnosis and progression. <h3>References</h3> Stanford and Bottini. Nat Rev Rheumatol 2014, 10(10):602–11. Messemaker et al. J Autoimmun 2015, 64:74–81. Ronninger et al. Genome Med 2012;4(1):2. Díaz-Gallo and Martín. Genome Med 2012;4(2):13. <h3>Acknowledgements</h3> This study was supported by European Union FEDER funds and "Fondo de Investigaciόn Sanitaria" (PI12/00060 and PI15/00525) from "Instituto de Salud Carlos III" (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 and RD16/0012 (RIER) from ISCIII. SR-M is supported by fund from the RETICS Program (RIER) (RD16/0012/0009). FG is a recipient of a Sara Borrell postdoctoral fellowship from ISCII (CD15/00095). RL-M is supported by a "Miguel Servet tipo-I" contract from ISCIII (CP16/00033). BU is supported by funds from the RETICS Program (RIER) (RD12/0009/0013) from ISCIII (Health Ministry, Spain). <h3>Disclosure of Interest</h3> None declared