PTPN22 1858 C/T polymorphism is associated with alteration of cytokine profiles as a potential pathogenic mechanism in rheumatoid arthritis

Abstract Introduction Rheumatoid arthritis (RA) is one of the most common prevalent autoimmune diseases. The 1858C/T (rs2476601) single nucleotide polymorphism (SNP) within the PTPN22 gene has been associated with susceptibility to inflammatory based diseases in several populations. It is implicated that altered cytokine production has a potential pathogenic role in the development of RA. The aim of this work was to analyze the association of 1858C/T PTPN22 polymorphism in RA patients with cytokine profiles. Materials and Methods This study was performed on 120 RA patients who were referred to the Rheumatology Research Centre, Shariati Hospital (Tehran, Iran), and 120 healthy controls. Genomic DNA was extracted and genotyped for 1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ as well as Anti-CCP and RF was measured by ELISA method. Results Results showed that 1858C/T PTPN22 SNP significantly (P =  0.007, OR = 2.321, 95% CI = 1.063–5.067) associated with RA. The 1858 T allele frequency was also significantly increased in RA patients in comparison to the controls (P =  0.008, OR = 3.583, 95% CI = 1.3-9.878). Our data demonstrated a significant reduction of IL-4 and IL-10 in PTPN22 1858C/T compared to 1858C/C RA patients. In addition, upregulation of IL-6, IFN-γ, and TNF-α was observed in PTPN22 1858C/T vs. 1858C/C RA patients. Discussion Our findings implicate altered cytokine profiles as a possible pathogenic mechanism by which the 1858 T allele may contribute to the progress of RA.