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Associations between the PTPN22 1858CT polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: results from a 10-year longitudinal study

Benedicte A Lie¹, Marte K Viken¹, Sigrid Ødegård², Désirée van der Heijde³, Robert Landewé³, Till Uhlig², Tore K Kvien²

¹ Institute of Immunology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
² Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
³ Department of Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands

Benedicte A Lie, Institute of Immunology, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway; b.a.lie{at}medisin.uio.no

Objective: 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 patients with RA (the EURIDISS cohort) was genotyped for the PTPN22 1858CT polymorphism. Radiographic damage was assessed by hand radiographs at baseline and after 1, 2, 5 and 10 years, and the radiographs were scored with the Sharp method modified by van der Heijde (Sharp–van der Heijde score) by a single experienced reader. Baseline serum levels of rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies were also examined.

Results: The reported association between RA susceptibility and carriage of the T allele (34.4% in patients vs 21.4% in controls; odds ratio 1.92, 95% confidence interval 1.36 to 2.71, p = 0.0002) was confirmed. An association between annual progression rate of Sharp–van der Heijde score and T-allele carriers (p = 0.01),was also found, which was also present when only patients positive for the shared epitope were analysed (p = 0.03). This association was also maintained in multivariate analyses adjusting for shared epitope and demographic variables.

Conclusions: An association between the PTPN22 risk variant and increased progression rate for structural damage was found. The results indicate that the PTPN22 gene may not only be associated with disease susceptibility, but also with disease progression.

Abbreviations: ACR, American College of Rheumatology; ANOVA, analysis of variance; CCP, cyclic citrullinated peptide; EURIDISS, European Research on Incapacitating Disease and Social Support; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; JSN, joint-space narrowing; PTPN22, protein tyrosine phosphatase N22; RA, rheumatoid arthritis; RF, rheumatoid factor; SE, shared epitope

Keywords: rheumatoid arthritis; PTPN22; longitudinal study; radiographic damage; genetic predisposition

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