IRAK2 and TLR10 confer risk of Hashimoto's disease: a genetic association study based on the Han Chinese population
IRAK2 and TLR10 confer risk of Hashimoto's disease: a genetic association study based on the Han Chinese population
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IRAK2 和 TLR10 赋予桥本氏病的风险：基于中国汉族人群的遗传关联研究
DOI：
10.1038/s10038-019-0613-5
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发表时间：
2019-07-01
影响因子：
3.5
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
--
作者：
Li, Miao;Han, Wei;Zhou, Qi
桥本氏病（HD）是自身免疫性甲状腺疾病的主要临床亚型之一。环境和遗传因素均有助于 HD 的发病机制。先前的证据表明IRAK2和TLR10都是HD的潜在候选易感基因。在这项研究中，总共招募了 3654 名中国女性，其中包括 973 名 HD 病例和 2681 名健康对照者。对 IRAK2 和 TLR10 中的 33 个标签单核苷酸多态性 (SNP) 进行了基因分型。在单标记和单倍型水平上进行遗传关联分析。还在仅病例样本中进行了基因间相互作用分析，并根据从 GTEx 数据库提取的数据对重要 SNP 进行了 eQTL 分析。我们确定了两个 SNP，rs165501（OR = 1.20，P = 0.0008，IRAK2）和 rs10004195（OR = 1.23，P = 0.0001，TLR10），被确定与 HD 显着相关。 Rs10004195与人垂体组织中TLR10基因表达显着相关(P = 2.00 x 10(-4)),而rs165501与人甲状腺组织中IRAK2表达显着相关(P = 3.10 x 10(-6))。基因间相互作用分析没有获得显着结果。我们的研究结果表明，IRAK2 和 TLR10 在 HD 的发生和发展中发挥着重要作用。
Hashimoto's disease (HD) is one of the major clinical subtypes of autoimmune thyroid disease. Both environmental and genetic factors contribute to the pathogenesis of HD. Previous evidence has shown that both IRAK2 and TLR10 are potential candidate susceptibility genes for HD. In this study, a total of 3654 Chinese women, including 973 HD cases and 2681 healthy controls, were recruited. Thirty-three tag single nucleotide polymorphisms (SNPs) in IRAK2 and TLR10 were genotyped. Genetic association analyses at both the single-marker and haplotype levels were performed. Gene-by-gene interaction analyses were also conducted in case-only samples, as well as eQTL analyses for significant SNPs based on data extracted from the GTEx database. We identified that two SNPs, rs165501 (OR = 1.20, P = 0.0008, IRAK2) and rs10004195 (OR = 1.23, P = 0.0001, TLR10), were identified to be significantly associated with HD. Rs10004195 was significantly associated with the gene expression of TLR10 in human pituitary tissues (P = 2.00 x 10(-4)), while rs165501 was significantly associated with the expression of IRAK2 in human thyroid tissues (P = 3.10 x 10(-6)). No significant results were obtained in the gene-by-gene interaction analyses. Our findings suggest that both IRAK2 and TLR10 play important roles in the onset and development of HD.