Background:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction of exocrine glands secondary to lymphocytic infiltration. Lymphoid tyrosine phosphatase (LYP) regulates T and B lymphocyte activation.PTPN22gene encodes LYP; multiple polymorphic variants have been described as genetic risk factor of autoimmune diseases.Objectives:The aim was to analyze thePTPN22rs2488457G>C, rs33996649G>A, and rs2476601C>T genetic variants relationship with the development risk of pSS in the western Mexico population.Methods:One hundred and eighty healthy subjects (HS) and 150 pSS patients, classified according to EULAR 2016 criteria, were included. The genetic variants and mRNA expression were determined through PCR-RFLP and qPCR assays.Results:The frequency of heterozygote rs33996649GA genotype was higher in pSS patients than HS [OR=3.143 (1–10.234), p=0.046], and also, rs33996649GA genotype was associated with high SSDAI score (p=0.01). The pSS patients showed 44-fold more mRNA expression in comparison with HS (p=0.002), and mRNA expression correlates with SSDAI (r2=0.512, p=0.006).Conclusion:The rs33996649G>A genetic variant of thePTPN22gene is associated with increased development risk of pSS in the western Mexican population. The expression mRNA correlates with disease activity in pSS.References:[1]Brito-Zerón, P., Baldini, C., Bootsma, H., Bowman, S. J., Jonsson, R., Mariette, X., Ramos-Casals, M. (2016). Sjögren syndrome.Nature Reviews Disease Primers, 2(July), 1–20.https://doi.org/10.1038/nrdp.2016.47[2]Stanford, S. M., & Bottini, N. (2014). PTPN22: The archetypal non-HLA autoimmunity gene.Nature Reviews Rheumatology,10(10), 602–611.https://doi.org/10.1038/nrrheum.2014.109[3]Chen, Z., Zhang, H., Xia, B., Wang, P., Jiang, T., Song, M., & Wu, J. (2013). Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis.International Journal of Colorectal Disease,28(10), 1351–1358.https://doi.org/10.1007/s00384-013-1671-3[4]Machado-Contreras, J. R., Muñoz-Valle, J. F., Cruz, A., Salazar-Camarena, D. C., Marín- Rosales, M., & Palafox-Sánchez, C. A. (2016b). Distribution of PTPN22 polymorphismsin SLE from western Mexico: correlation with mRNA expression and disease activity.Clinical and Experimental Medicine,16(3), 399–406.https://doi.org/10.1007/s10238-015-0359-0Disclosure of Interests:None declared