The <Emphasis Type="Italic">PTPN22</Emphasis>1858C/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden |
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Authors: | Heidi Kokkonen Martin Johansson Lena Innala Erik Jidell Solbritt Rantapää-Dahlqvist |
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Institution: | 1.Department of Rheumatology, University Hospital, SE-901 85 Umeå, Sweden;2.Department of Transfusion Medicine, University Hospital, SE-901 85 Umeå, Sweden |
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Abstract: | 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 (χ2 = 23.84, P = 0.000001, odds ratio = 1.69, 95% confidence interval = 1.36–2.11; and χ2 = 22.68, P = 0.000002, 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. |
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