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Associations between the PTPN22 1858C>T polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: Results from a 10-year longitudinal study
  1. Benedicte A Lie (b.a.lie{at}
  1. Rikshospitalet-Radiumhospitalet Medical Center, Norway
    1. Marte K Viken (m.k.viken{at}
    1. Rikshospitalet-Radiumhospitalet Medical Center, Norway
      1. Sigrid Ødegård (sigrid.odegard{at}
      1. Diakonhjemmet hospital, Norway
        1. Désirée van der Heijde (dhe{at}
        1. University Hospital Maastricht, Netherlands
          1. Robert Landewé (rlan{at}
          1. University of Maastricht, Netherlands
            1. Till Uhlig (till.uhlig{at}
            1. Diakonhjemmet hospital, Norway
              1. Tore K Kvien (t.k.kvien{at}
              1. Diakonhjemme hospital, Norway


                Objectives: The aim of this study was to investigate whether the PTPN22 1858T risk variant is associated with the rate of radiographic progression in rheumatoid arthritis (RA).

                Methods: A longitudinally followed cohort of 238 Norwegian RA patients (the EURIDISS cohort) was genotyped for the PTPN22 1858C>T polymorphism. Radiographic damage was assessed by hand radiographs at baseline, after 1, 2, 5 and 10 years, and the radiographs were scored with the van der Heijde modified Sharp method (vdH Sharp score) by one experienced reader. Baseline serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were also examined.

                Results: We confirmed the reported association between RA susceptibility and carriage of the T-allele (34.4% in patients vs. 21.4% in controls; OR=1.92 (1.36-2.71), p= 0.0002). We also found an association between annual progression rate of vdH Sharp score and T-allele carriers (p=0.01), which was also present when only patients positive for the shared epitope were analysed (p=0.03). This association was also maintained in multitvariate analyses adjusting for shared epitope and demographic variables.

                Conclusions: An association between the PTPN22 risk variant and increased progression rate for structural damage was observed. Our finding indicates that the PTPN22 gene may not only be associated with disease susceptibility, but also with disease progression.

                • PTPN22
                • genetic predisposition
                • longitudinal study
                • radiographic damage
                • rheumatoid arthritis

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