The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases
The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases
复制标题
DOI：
10.1136/ard.2008.106567
复制
发表时间：
2010-04-01
影响因子：
27.4
通讯作者：
Martin, Javier
中科院分区：
文献类型：
--
作者：
Kurreeman, Fina A. S.;Goulielmos, George N.;Martin, Javier
目的TRAF 1-C5基因座是类风湿关节炎（RA）的一个遗传危险因子。由于遗传风险因素往往与几种自身免疫性疾病重叠，因此进行了一项研究以调查该区域是否与1型糖尿病（TID）、乳糜泻（CD）、系统性硬化症（SSc）和系统性红斑狼疮（SLE）相关。367例SSc，746例SLE和3494例种族和地理匹配的健康个体。结果rs 10818488 A等位基因与T1 D有显著相关性，其中T1 D患者99例，SLE患者272例，健康人482例（OR 1.14，p=0.027）和SLE（OR 1.16，p=0.016），这在来自克里特岛的99名T1 D患者、272名SLE患者和482名对照者中重复（分别为OR 1.64，p=0.002; OR 1.43，p=0.002）。对所有T1 D患者（N=961）和所有SLE患者（N=1018）与3976名健康个体进行联合分析，得出等位基因共同OR分别为1.19（p=0.002）和1.22（p=2.6x10 - 4）。然而，将我们的数据集与来自WTCCC的T1 D样本集相结合，导致无显著相关性（OR 1.06，p=0.087）。相反，SLEGEN研究的先前未发表的结果显示，同一等位基因与（OR 1.19，p=0.0038），总体效应为1.22（p= 1.02 × 10（-6））。结论TRAF 1-C5基因座与SLE的发生、发展及预后密切相关，这意味着该区域位于与多种自身免疫性疾病相关的通路中。
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 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=2.6x10(-4)), respectively. However, combining our dataset with the T1D sample set from the WTCCC resulted in a nonsignificant 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 In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02x10(-6)) in a total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.