TY - JOUR
T1 - The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases
AU - Kurreeman, F.A.
AU - Goulielmos, G.N.
AU - Alizadeh, B.Z.
AU - Rueda, B.
AU - Houwing-Duistermaat, JJ
AU - Sanchez, E.
AU - Bevova, M.R.
AU - Radstake, T.R.
AU - Vonk, M.C.
AU - Galanakis, E.
AU - Ortego, N.
AU - Verduyn, W.
AU - Zervou, M.I.
AU - Roep, B.O.
AU - Dema, B.
AU - Espino, L.
AU - Urcelay, E.
AU - Boumpas, D.T.
AU - van den Berg, L.H.
AU - Wijmenga, C.
AU - Koeleman, B.P.C.
AU - Huizinga, T.W.
AU - Toes, R.E.
AU - Martin, J.
PY - 2010/4
Y1 - 2010/4
N2 - 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 In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02 x 10(-6)) in a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.
AB - 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.
KW - Autoimmune Diseases
KW - Celiac Disease
KW - Chromosomes, Human, Pair 9
KW - Diabetes Mellitus, Type 1
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Lupus Erythematosus, Systemic
KW - Polymorphism, Single Nucleotide
KW - Scleroderma, Systemic
KW - TNF Receptor-Associated Factor 1
KW - Journal Article
KW - Meta-Analysis
KW - Multicenter Study
KW - Research Support, Non-U.S. Gov't
U2 - 10.1136/ard.2008.106567
DO - 10.1136/ard.2008.106567
M3 - Article
C2 - 19433411
SN - 0003-4967
VL - 69
SP - 696
EP - 699
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 4
ER -