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The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases.
  1. Fina AS Kurreeman (b.a.s.kurreeman{at}lumc.nl)
  1. LUMC, Netherlands
    1. George N Goulielmos (goulielmos{at}med.uoc.gr)
    1. University of Crete, Greece
      1. Behrooz Z Alizadeh (b.z.alizadeh{at}umcutrecht.nl)
      1. University Medical Center Utrecht, Netherlands
        1. Blanca Rueda (blarume{at}ipb.csic.es)
        1. Consejo Superior de Investigaciones Científicas, Spain
          1. Jeanine Houwing-Duistermaat (j.j.houwing{at}lumc.nl)
          1. LUMC, Netherlands
            1. Elena Sánchez (elena{at}ipb.csic.es)
            1. Consejo Superior de Investigaciones Científicas, Spain
              1. Marianna Bevova (m.bevova{at}umcutrecht.nl)
              1. University Medical Center Utrecht, Netherlands
                1. Timothy R Radstake (t.radstake{at}aig.umcn.nl)
                1. Radboud University Nijmegen Medical Center, Netherlands
                  1. Madelon C Vonk (m.vonk{at}reuma.umcn.nl)
                  1. Radboud University Nijmegen Medical Center, Netherlands
                    1. Emmanouil Galanakis (egalanak{at}med.uoc.gr)
                    1. University of Crete, Greece
                      1. Norberto Ortego (nortego{at}telefonica.net)
                      1. Hospital Clínico San Cecilio, Spain
                        1. Willem Verduyn (w.verduyn{at}lumc.nl)
                        1. LUMC, Netherlands
                          1. Maria I Zervou (mzervou{at}med.uoc.gr)
                          1. University of Crete, Greece
                            1. SLEGEN Consortium
                            1. -, United States
                              1. Bart O Roep (b.o.roep{at}lumc.nl)
                              1. LUMC, Netherlands
                                1. Barbara Dema (bdmapott{at}hotmail.com)
                                1. Hospital Clínico San Cecilio, Spain
                                  1. Laura Espino (lauraep80{at}yahoo.es)
                                  1. Hospital Clínico San Cecilio, Spain
                                    1. Elena Urcelay (eurcelay.hcsc{at}salud.madrid.org)
                                    1. Hospital Clínico San Carlos, Madrid, Spain
                                      1. Dimitri T Boumpas (boumpasd{at}med.uoc.gr)
                                      1. University of Crete, Greece
                                        1. Leonard H van den Berg (l.h.vandenberg{at}umcutrecht.nl)
                                        1. University Medical Center Utrecht, Netherlands
                                          1. Ciska Wijmenga (c.wijmenga{at}medgen.umcg.nl)
                                          1. University Medical Center Utrecht, Netherlands
                                            1. Bobby PC Koeleman (b.p.c.koeleman{at}umcutrecht.nl)
                                            1. University Medical Center Utrecht, Netherlands
                                              1. Tom W J Huizinga (t.w.j.huizinga{at}lumc.nl)
                                              1. LUMC, Netherlands
                                                1. Rene E M Toes (r.e.m.toes{at}lumc.nl)
                                                1. LUMC, Netherlands
                                                  1. Javier Martin (martin{at}ipb.csic.es)
                                                  1. Consejo Superior de Investigaciones Científicas, Spain

                                                    Abstract

                                                    Objectives: The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis. Since genetic risk factors tend to overlap with several autoimmune diseases, we aimed to investigate whether this region is associated with Type I Diabetes (TID), Celiac Disease (CD), Systemic Sclerosis (SSc) and Systemic Lupus Erythematosus (SLE).

                                                    Methods: We genotyped the most consistently associated SNP, rs10818488, in a total of 735 T1D, 1049 CD, 367 SSc, 746 SLE and 3494 ethnically and geographically matched healthy individuals. The replication sample set consisted of 99 T1D, 272 SLE patients and 482 healthy individuals from Crete.

                                                    Results: We detected significant association of the rs10818488 A allele with T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016) which was replicated in 99 T1D, 272 SLE patients and 482 controls from Crete (OR 1.64, p=0.002; OR 1.43, p=0.002 respectively). Joint analysis of all T1D (N=961) and all SLE (N=1018) patients compared to 3976 healthy individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22 (P=2.6x10-4) respectively. However, combining our dataset with the T1D sample set from the WTCCC results in a non-significant association (OR 1.06, p=0.087). In contrast, previously unpublished results from the SLEGEN study shows significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02x10-6) in a total of 1577 SLE patients and 4215 healthy individuals.

                                                    Conclusion: We report significant association of the TRAF1-C5 locus in SLE implying that this region lies in a pathway relevant to multiple autoimmune diseases.

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