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The TNF Receptor Superfamily member 1b 676T>G polymorphism in relation to response to infliximab and adalimumab treatment and disease severity in rheumatoid arthritis
  1. Erik J.M. Toonen (e.toonen{at}antrg.umcn.nl)
  1. Radboud University Nijmegen Medical Centre, Netherlands
    1. Marieke J.H. Coenen (m.coenen{at}antrg.umcn.nl)
    1. Radboud University Nijmegen Medical Centre, Netherlands
      1. Wietske Kievit (w.kievit{at}reuma.umcn.nl)
      1. UMC Nijmegen, Netherlands
        1. Jaap Fransen (j.fransen{at}reuma.umcn.nl)
        1. Radboud University Nijmegen Medical Centre, Netherlands
          1. Agnes M.M. Eijsbouts (a.eijsbouts{at}maartenskliniek.nl)
          1. St Maartenskliniek Nijmegen, Netherlands
            1. Hans Scheffer (h.scheffer{at}antrg.umcn.nl)
            1. Radboud University Nijmegen Medical Centre, Netherlands
              1. Timothy R.D.J. Radstake (t.radstake{at}reuma.umcn.nl)
              1. University Medical Center Nijmegen, Netherlands
                1. Marjonne C.W. Creemers (m.creemers{at}reuma.umcn.nl)
                1. UMC Nijmegen, Netherlands
                  1. Dirk-Jan R.A.M. de Rooij (dj.derooij{at}maartenskliniek.nl)
                  1. St Maartenskliniek Nijmegen, Netherlands
                    1. Piet L.C.M. van Riel (p.vanriel{at}reuma.umcn.nl)
                    1. University Medical Center Nijmegen, Netherlands
                      1. Barbara Franke (b.franke{at}antrg.umcn.nl)
                      1. University Medical Center Nijmegen, Netherlands
                        1. P Barrera (p.barrera{at}reuma.umcn.nl)
                        1. UMC Nijmegen, Netherlands

                          Abstract

                          Objective: The purpose of this study was to assess the effect of a functional polymorphism (676T>G, M196R) in the Tumor Necrosis Factor Receptor super family 1b (TNFSF1b) gene on disease activity, radiologic joint damage and response to infliximab and adalimumab therapy in patients with rheumatoid arthritis (RA).

                          Methods: Two RA patient cohorts were genotyped for the 676T>G polymorphism (rs1061622) in exon 6 of the TNFSF1b gene by restriction fragment length polymorphism analysis. One cohort (n=234) included patients from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register with detailed information on their response to anti-TNF therapy (infliximab and adalimumab), the other concerned patients from a long-term observational early inception cohort at our center (n=248).

                          Results: The 676T>G polymorphism was not associated with anti-TNF response after three or six months of therapy. Linear regression analysis showed no significant difference in the progression of radiologic joint damage during the first three and six years of disease between the three genotype groups (TT, TG and GG). No difference in mean disease activity between genotypes was observed after three and six years of disease, either.

                          Conclusion: Despite its demonstrated functionality, the 676T>G polymorphism in the TNFSF1b gene does not play a major role in either the response to anti-TNF therapy or in the disease severity or radiologic progression in RA.

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