甲状腺球蛋白基因的精细定位确定了中国汉族人群中Graves病的两个独立风险位点。
Fine mapping of thyroglobulin gene identifies two independent risk loci for Graves' disease in Chinese Han population.
作者信息
Xuan Miao, Zhao Shuang-Xia, Yan Chen-Yan, Yang Jun, Li Ying, Song Li-Ge, Song Huai-Dong, Zhang Xiu-Zhen
机构信息
Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai 200011, China.
出版信息
Ann Transl Med. 2019 Sep;7(18):434. doi: 10.21037/atm.2019.08.115.
BACKGROUND
This study aimed to determine independent risk loci of Graves' disease (GD) in the thyroglobulin (TG) region.
METHODS
In this two-staged association study, a total of 9,757 patients with GD and 10,626 sex-matched controls were recruited from Chinese Han population. Illumina Human660-Quad BeadChips in the discovery stage and TaqMan SNP Genotyping Assays in the replication stage were used for genotyping. Trend test and logistic regression analysis were performed in this association study.
RESULTS
In the discovery stage, rs2294025 and rs7005834 were the most highly associated susceptibility loci with GD in . In the replication phase, 7 SNPs, including rs2294025 and rs7005834, were selected for fine-mapping. Finally, we confirmed that rs2294025 and rs7005834 were the independent risk loci of GD in the combined populations. At the same time, there was no significant difference between the risk allele frequencies of rs2294025 and rs7005834 in different clinical phenotypes of GD.
CONCLUSIONS
The fine mapping study of thyroglobulin identified two independent SNPs (rs2294025 and rs7005834) for GD susceptibility. However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody. These results provide a deeper understanding of the association mechanism of and GD risk.
背景
本研究旨在确定甲状腺球蛋白（TG）区域中格雷夫斯病（GD）的独立风险位点。
方法
在这项两阶段关联研究中，从中国汉族人群中招募了总共9757例GD患者和10626例性别匹配的对照。发现阶段使用Illumina Human660-Quad BeadChips，复制阶段使用TaqMan SNP基因分型检测进行基因分型。在这项关联研究中进行了趋势检验和逻辑回归分析。
结果
在发现阶段，rs2294025和rs7005834是与GD关联度最高的易感位点。在复制阶段，选择了包括rs2294025和rs7005834在内的7个单核苷酸多态性（SNP）进行精细定位。最后，我们证实rs2294025和rs7005834是合并人群中GD的独立风险位点。同时，rs2294025和rs7005834的风险等位基因频率在GD的不同临床表型之间没有显著差异。
结论
甲状腺球蛋白的精细定位研究确定了两个与GD易感性相关的独立单核苷酸多态性（rs2294025和rs7005834）。然而，在GD的不同临床表型之间，包括性别、格雷夫斯眼病（GO）以及促甲状腺素受体抗体、甲状腺过氧化物酶抗体和甲状腺球蛋白抗体的血清水平，未观察到rs2294025和rs7005834有显著差异。这些结果为TG与GD风险的关联机制提供了更深入的理解。
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