title: The PTPN22 1858C/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden.
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 (chi2 = 23.84, P = 0.000001, odds ratio = 1.69, 95% confidence interval = 1.36-2.11; and chi2 = 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.
authors.affiliation: Department of Rheumatology, University Hospital, SE-901 85 Umeå, Sweden.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kokkonen
authors.forename: Martin
authors.initials: M
authors.lastname: Johansson
authors.forename: Lena
authors.initials: L
authors.lastname: Innala
authors.forename: Erik
authors.initials: E
authors.lastname: Jidell
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
mesh_terms: D017668:Age of Onset; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D013548:Sweden
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22