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Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis
  1. Hans Ulrich Scherer (h.u.scherer{at}lumc.nl)
  1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
    1. Michael PM van der Linden (m.p.m.van_der_linden{at}lumc.nl)
    1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
      1. Fina A S Kurreeman (b.a.s.kurreeman{at}lumc.nl)
      1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
        1. Gerrie Stoeken-Rijsbergen (g.stoeken-rijsbergen{at}lumc.nl)
        1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
          1. Saskia le Cessie (s.le_cessie{at}lumc.nl)
          1. Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, Netherlands
            1. Tom W J Huizinga (t.w.j.huizinga{at}lumc.nl)
            1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
              1. Annett H M van der Helm-van Mil (a.h.m.van_der_helm{at}lumc.nl)
              1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
                1. René E M Toes (r.e.m.toes{at}lumc.nl)
                1. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands

                  Abstract

                  Objective: Two novel genetic polymorphisms on chromosome 6q23 are associated with sus-ceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumor necrosis factor α-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NFκB and as such involved in inhibiting TNF-Receptor mediated signalling effects. Interestingly, the initial associations were detected in patients with long-standing RA. However, no association was found for rs10499194 in a Swedish early arthritis cohort. As this could be caused by overrepresentation of patients with severe disease in cohorts with long-standing RA, we analyzed the effect of the 6q23 region on the rate of joint destruction.

                  Methods: Five single nucleotide polymorphisms (SNPs) in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated to progression of radiographic joint damage for a follow-up time of 5 years.

                  Results: Two polymorphisms (rs675520 and rs9376293) associated with severity of radio-graphic joint damage in ACPA+ patients. Importantly, the effects were present after correc-tion for confounding factors such as secular trends in treatment.

                  Conclusions: Our data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.

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