Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease
Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease
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DOI：
10.1210/jc.2004-2148
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发表时间：
2005-05-01
影响因子：
5.8
通讯作者：
Akamizu, T
中科院分区：
文献类型：
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作者：
Hiratani, H;Bowden, DW;Akamizu, T
我们之前使用 TSH 受体 (TSHR) 基因附近或内部的微卫星标记进行的研究揭示了日本患者的自身免疫性甲状腺疾病 (AITD) 与 TSHR 微卫星等位基因之间的显着关联。在本研究中，我们使用跨 TSHR 基因的间隔 3 - 50 kb 的单核苷酸多态性 (SNP) 进行了 AITD 的病例对照分析。我们观察到 AITD/格雷夫斯病 (GD)/桥本甲状腺炎与多个 SNP 之间存在显着关联。具体而言，TSHR 基因内含子 7 中的 SNP JST022302 和几个相邻的 SNP 与 GD 显着相关 (P = 0.039 - 0.0004)，但与桥本甲状腺炎无关。此外，我们通过连锁不平衡分析鉴定了内含子 7 周围的三个单倍型块。在单倍型病例对照分析中，包括 JST022302 在内的单倍型块中的单个 SNP 单倍型 [AATG(CT)(6)(TT) AG] 显示与 GD 显着相关（P = 0.0058）。这些发现表明 TSHR 基因内含子 7 的等位基因有助于 GD 易感性。
Our previous studies using microsatellite markers near or in the TSH receptor (TSHR) gene revealed significant association between autoimmune thyroid disease (AITD) in Japanese patients and TSHR microsatellite alleles. In the present study, we performed a case-control analysis of AITD using single-nucleotide polymorphisms ( SNPs) spaced 3 - 50 kb apart spanning the TSHR gene. We observed significant associations between AITD/Graves' disease (GD)/Hashimoto's thyroiditis and multiple SNPs. Specifically, the SNP JST022302 and several adjacent SNPs in intron 7 of the TSHR gene were significantly associated with GD ( P = 0.039 - 0.0004) but not Hashimoto's thyroiditis. Furthermore, we identified three haplotype blocks around intron 7 by linkage disequilibrium analysis. A single SNP haplotype [AATG(CT)(6)(TT) AG] in the haplotype block including JST022302 showed significant association with GD in haplotype case-control analysis ( P = 0.0058). These findings suggest that alleles of intron 7 of the TSHR gene contribute to GD susceptibility.