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  • Title: The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases.
    Author: Kurreeman FA, Goulielmos GN, Alizadeh BZ, Rueda B, Houwing-Duistermaat J, Sanchez E, Bevova M, Radstake TR, Vonk MC, Galanakis E, Ortego N, Verduyn W, Zervou MI, Roep BO, Dema B, Espino L, Urcelay E, Boumpas DT, van den Berg LH, Wijmenga C, Koeleman BP, Huizinga TW, Toes RE, Martin J, AADEA Group, SLEGEN Consortium.
    Journal: Ann Rheum Dis; 2010 Apr; 69(4):696-9. PubMed ID: 19433411.
    Abstract:
    OBJECTIVES: The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune diseases, a study was undertaken to investigate whether this region is associated with type 1 diabetes (TID), celiac disease (CD), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). METHODS: The most consistently associated SNP, rs10818488, was genotyped in a total of 735 patients with T1D, 1049 with CD, 367 with SSc, 746 with SLE and 3494 ethnically- and geographically-matched healthy individuals. The replication sample set consisted of 99 patients with T1D, 272 with SLE and 482 healthy individuals from Crete. RESULTS: A significant association was detected between the rs10818488 A allele and T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016), which was replicated in 99 patients with T1D, 272 with SLE and 482 controls from Crete (OR 1.64, p=0.002; OR 1.43, p=0.002, respectively). Joint analysis of all patients with T1D (N=961) and all patients with SLE (N=1018) compared with 3976 healthy individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22 (p=2.6 x 10(-4)), respectively. However, combining our dataset with the T1D sample set from the WTCCC resulted in a non-significant association (OR 1.06, p=0.087). In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02 x 10(-6)) in a total of 1577 patients with SLE and 4215 healthy individuals. CONCLUSION: A significant association was found for the TRAF1-C5 locus in SLE, implying that this region lies in a pathway relevant to multiple autoimmune diseases.
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