A C/T single-nucleotide polymorphism in the region of the CD40 gene is associated with Graves' disease
A C/T single-nucleotide polymorphism in the region of the CD40 gene is associated with Graves' disease
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DOI：
10.1089/105072502321085234
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发表时间：
2002-12-01
期刊：
影响因子：
6.6
通讯作者：
Greenberg, DA
中科院分区：
文献类型：
--
作者：
Tomer, Y;Concepcion, E;Greenberg, DA
格雷夫斯病（GD）是易感基因和环境因素相互作用的结果。我们以前绘制了一个易感基因GD染色体20 q11（GD-2），最近已独立复制。在20 q11定位的基因中，CD 40基因是一个重要的共刺激分子，也是GD的一个很好的位置候选基因。我们研究了20 q11上的CD 40基因是否是GD的易感基因。在高加索家庭的一个子集的连锁分析显示，在CD 40位点的最大多点对数的优势（LOD）得分为3.3。然后，我们对8名先证者和10名对照者的CD 40基因的所有9个外显子进行测序，并在CD 40基因的Kozak序列的-1位鉴定了一个新的C/T单核苷酸多态性（SNP）。在154例白人GD患者和118例白人对照中对CD 40 C/T-1 SNP进行病例对照关联分析，结果显示CC基因型与GD之间存在关联（p = 0.048，相对风险[RR] = 1.6）。此外，当仅使用来自连锁家族的先证者（n = 20）时，这种关联更强（p = 0.009，RR = 4.8）。传递不平衡检验（TDT）分析也显示CD 40 C/T-1 SNP的C等位基因优先传递给受影响的个体（p = 0.02）。总之，我们的研究结果表明，CD 40基因是一个新的易感基因，在某些家庭中的GD，因为它是连锁和相关的GD。
Graves' disease (GD) develops as a result of an interaction between susceptibility genes and environmental factors. We have previously mapped a susceptibility locus for GD on chromosome 20q11 (GD-2), which has recently been independently replicated. Among the genes mapped to 20q11 was the CD40 gene, an important costimulatory molecule and a good positional candidate gene for GD. We investigated whether the CD40 gene was the GD susceptibility gene on 20q11. Linkage analysis in a subset of Caucasian families showed a maximum multipoint logarithm of odds (LOD) score of 3.3 at the CD40 locus. We then sequenced all 9 exons of the CD40 gene in 8 probands and 10 controls and identified a new C/T single-nucleotide polymorphism (SNP) in the Kozak sequence of the CD40 gene at position -1. Case control association analysis of the CD40 C/T-1 SNP in 154 Caucasian patients with GD and 118 Caucasian controls showed an association between the CC genotype and GD (p = 0.048, relative risk [RR] = 1.6). Furthermore, the association was stronger when only the probands from the linked families (n = 20) were used (p = 0.009, RR = 4.8). Transmission disequilibrium test (TDT) analysis also showed preferential transmission of the C allele of the CD40 C/T-1 SNP to affected individuals (p = 0.02). In conclusion, our results suggested that the CD40 gene was a new susceptibility gene for GD within certain families because it was both linked and associated with GD.