Association of the TSHR gene with Graves' disease: the first disease specific locus
Association of the TSHR gene with Graves' disease: the first disease specific locus
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DOI：
10.1038/sj.ejhg.5201485
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发表时间：
2005-11-01
影响因子：
5.2
通讯作者：
Gough, SC
中科院分区：
文献类型：
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作者：
Dechairo, BM;Zabaneh, D;Gough, SC
自身免疫性甲状腺疾病（AITD）的发生与针对促甲状腺激素受体（TSHR）的自身抗体有关。以前的研究未能证明TSHR和AITD或其任何亚表型之间的一致关联。在本研究中，我们分析了包括TSHR在内的连锁不平衡（LD）结构，以确定LD“块”和SNP，它们捕获了大多数块内单倍型多样性。在1059例AITD白种人病例和971例白种人对照中，对单倍型标记SNP以及先前研究中报道的所有常见SNP进行基因分型。一个单倍型，跨越两个LD区组，显示与Graves病（GD）相关（P < 1 × 10（-6），OR 1.7），但与自身免疫性甲状腺功能减退症（AIH）无关。我们在一个由1366例AITD病例和1061例对照组成的英国高加索人队列中，通过对最相关的GD SNP rs 2268458进行基因分型，重复了这些发现（GD，P = 2 × 10（-6），OR 1.3; AIH，P = NS）。这些结果在两个独立的高加索数据集表明，TSHR是第一个复制的GD特异性位点值得进一步精细定位和功能分析，以确定病因变异。
The development of autoimmune thyroid disease (AITD) is associated with autoantibodies directed against the thyroid stimulating hormone receptor (TSHR). Previous studies have failed to demonstrate a consistent association between the TSHR and AITD, or any of its sub-phenotypes. In the present study, we analysed the linkage disequilibrium (LD) structure encompassing the TSHR, to identify LD 'blocks' and SNPs, which capture the majority of intra-block haplotype diversity. The haplotype tagging SNPs, plus all common SNPs reported in previous studies were genotyped in 1059 AITD Caucasian cases and 971 Caucasian controls. A haplotype, across two LD blocks, showed association (P < 1 x 10(-6), OR 1.7) with Graves' disease (GD) but not autoimmune hypothyroidism (AIH). We replicated these findings by genotyping the most associated GD SNP, rs2268458, in a separate UK Caucasian cohort of 1366 AITD cases and 1061 controls ( GD, P = 2 x 10(-6), OR 1.3; AIH, P = NS). These results in two independent Caucasian data sets suggest that the TSHR is the first replicated GD-specific locus meriting further fine mapping and functional analysis to identify the aetiological variants.