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The PTPN22 1858C/T polymorphism has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have shown that carriage of the T variant (CT or TT) of PTPN22 in combination with anti-cyclic citrullinated peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA. In the present study we analysed the association between the PTPN22 1858C/T polymorphism and early RA in patients from northern Sweden, related the polymorphism to autoantibodies and the HLA-DR shared epitope, and analysed their association with markers for disease activity and progression. The inception cohort includes individuals who also donated samples before disease onset. A case-control study was performed in patients (n = 505; 342 females and 163 males) with early RA (mean duration of symptoms = 6.3 months) and in population-based matched controls (n = 970) from northern Sweden. Genotyping of the PTPN22 1858C/T polymorphism was performed using a TaqMan instrument. HLA-shared epitope alleles were identified using PCR sequence-specific primers. Anti-CCP2 antibodies were determined using enzyme-linked immunoassays. Disease activity (that is, the number of swollen and tender joints, the global visual analogue scale, and the erythrocyte sedimentation rate) was followed on a regular basis (that is, at baseline and after 6, 12, 18 and 24 months). Both the 1858T allele and the carriage of T were associated with RA (chi2 = 23.84, P = 0.1, odds ratio = 1.69, 95% confidence interval = 1.36-2.11; and chi2 = 22.68, P = 0.2, odds ratio = 1.79, 95% confidence interval = 1.40-2.29, respectively). Association of the 1858T variant with RA was confined to seropositive disease. Carriage of 1858T and the presence of anti-CCP antibodies was independently associated with disease onset at an earlier age (P < 0.05 and P < 0.01, respectively), while the combination of both resulted in an even earlier age at onset. Smoking was identified as a risk factor independent of the 1858T variant and anti-CCP antibodies.

arthritis research and therapy

Correction: The PTPN22 1858C/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden