在一个大型队列中的遗传研究支持 Graves 病和桥本甲状腺功能减退症的不同发病机制。
Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism.
机构信息
The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostic and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
J Clin Endocrinol Metab. 2020 Jul 1;105(7). doi: 10.1210/clinem/dgaa170.
CONTEXT
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases.
OBJECTS
To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT.
DESIGN
In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age.
RESULTS
We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10-8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed.
CONCLUSION
Our findings suggested that the pathogenesis of HT and GD was different.
背景
桥本甲状腺炎（HT）和格雷夫斯病（GD）是两种主要的自身免疫性甲状腺疾病，它们既有相似之处，也有不同之处。确定将 HT 与 GD 区分开来的遗传基础对于更好地理解这两种密切相关的疾病之间的差异至关重要。
目的
在中国人群中鉴定 HT 的易感基因，并比较 GD 和 HT 之间的易感基因。
设计
在本研究中，选择了来自 18 个已建立的 GD 风险位点的 18 个 SNP，然后对 2682 例 HT 患者、4980 例 GD 患者和 3892 例对照进行基因分型。在 SPSS 上对 HT 与对照之间的关联分析和 HT 与 GD 之间的异质性分析进行了分析，使用 logistic 回归分析调整了性别和年龄。
结果
我们在中国汉族人群中鉴定出 11 个 HT 的易感基因位点，其中包括 SLAMF6 基因座中的 rs1265883、CTLA4 中的 rs1024161、HLA-B 中的 rs1521 和 X 染色体上的 rs5912838 在内的 4 个基因座，达到了全基因组意义上的 5×10-8。其中 5 个基因座是首次与 HT 相关。我们还鉴定出了 6 个 GD 和 HT 之间存在异质性的易感基因位点。其中，4 个基因座与 GD 相关但与 HT 无关，包括 HLA-DPB1、CD40、TSHR 和 TG；HLA-B 与 GD 的关联强于与 HT 的关联，但 SLAMF6 的关联相反。
结论
我们的研究结果表明，HT 和 GD 的发病机制不同。
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