Association of the interleukin-2 receptor alpha (IL-2Rα)/CD25 gene region with Graves' disease using a multilocus test and tag SNPs
Association of the interleukin-2 receptor alpha (IL-2Rα)/CD25 gene region with Graves' disease using a multilocus test and tag SNPs
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DOI：
10.1111/j.1365-2265.2007.02762.x
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发表时间：
2007-04-01
影响因子：
3.2
通讯作者：
Gough, Stephen C. L.
中科院分区：
文献类型：
--
作者：
Brand, Oliver J.;Lowe, Christopher E.;Gough, Stephen C. L.
目的 少数免疫反应基因一直与常见的自身免疫性疾病相关。最近，一种使用标签单核苷酸多态性（SNP）的连锁不平衡（LD）作图方法，确定了1型糖尿病（T1D）与10p15号染色体上的白细胞介素 - 2受体α（IL - 2Rα）/CD25基因区域之间的遗传关联。由于某些自身免疫性疾病，如自身免疫性甲状腺疾病（AITD）和T1D在某些家族中聚集在一起，我们试图确定与T1D相关的CD25区域是否也与格雷夫斯病（GD）相关。
设计 我们对20个标签SNP进行了病例 - 对照关联研究。
患者 从英国的7个主要中心收集了1896例GD患者，并从1958年英国出生队列中选取了1822例地理位置匹配的对照。
测量 使用多位点检验分析20个标签SNP，以确定GD与CD25区域之间的关联。计算标签SNP的比值比（OR），以便与先前T1D的结果进行比较。
结果 多位点检验提供了GD与CD25区域之间存在关联的统计学证据（P = 4.5×10⁻⁴），20个标签SNP的关联模式与在T1D中发现的相似。
结论 与GD的关联以及先前报道的与T1D的关联表明，CD25区域是自身免疫性疾病的一个普遍易感位点，并且与IL - 2受体途径在T细胞在自身免疫控制中的发育和功能中起主要作用是一致的。
Objective A small number of immune response genes have been consistently associated with the common autoimmune conditions. Recently, a linkage disequilibrium (LD) mapping approach, using tag single nucleotide polymorphisms (SNPs), identified genetic association between type 1 diabetes (T1D) and the interleukin-2 receptor alpha (IL-2R alpha)/CD25 gene region on chromosome 10p15. Because certain autoimmune diseases, such as autoimmune thyroid disease (AITD) and T1D cluster together in certain families, we sought to determine if the TID-associated CD25 region was also associated with Graves' disease (GD).Design We performed a case-control association study of 20 tag SNPs.Patients 1896 GD patients were collected from seven major centres in the UK and 1822 geographically matched controls from the 1958 British Birth Cohort.Measurements The 20 tag SNPs were analysed using a multilocus test to identify an association between GD and the CD25 region. Odds ratios (ORs) were calculated for the tag SNPs, allowing a comparison with previous results for T1D.Results The multilocus test provided statistical evidence of an association between GD and the CD25 region (P = 4.5 x 10(-4)), with the pattern of association of the 20 tag SNPs similar to that found in T1D.Conclusions Association with GD, as well as that previously reported with T1D, suggests that the CD25 region is acting as a general susceptibility locus for autoimmune disease, and is consistent with a major role for the IL-2-receptor pathway in the development and function of T cells in the control of autoimmunity.