Candidate gene associations reveal sex-specific Graves' disease risk alleles among Chinese Han populations
Candidate gene associations reveal sex-specific Graves' disease risk alleles among Chinese Han populations
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候选基因关联揭示中国汉族人群中性别特异性格雷夫斯病风险等位基因
DOI：
10.1002/mgg3.1249
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发表时间：
2020
影响因子：
2
通讯作者：
Song Huai-Dong
中科院分区：
文献类型：
--
作者：
Yan Chen-Yan;Ma Yu-Ru;Sun Feng;Zhang Rui-Jia;Fang Ya;Zhang Qian-Yue;Wu Feng-Yao;Zhao Shuang-Xia;Song Huai-Dong
背景：通过病例对照关联研究发现了几种易感性单核苷酸多态性，Graves病是最常见的自身免疫性甲状腺疾病之一。在这项研究中，我们旨在确定在中国汉族人群中是否存在观察到的遗传关联差异受到性别的影响。方法共纳入8835例Graves病患者和9936例性别匹配的健康对照者。通过两阶段关联分析证实，对20个Graves病易感位点进行了性别特异性分析。结果gpr174和itm2基因主要在Xq21.1位点的rs5912838位点检测到显著的性别-基因相互作用，男性Graves病患者的风险等位基因频率明显高于女性。有趣的是，与女性相比，男性格雷夫斯病患者在接受抗甲状腺药物治疗至少1年后具有更高的累积遗传风险和更高的持续促甲状腺激素受体抗体阳性率。结论本研究结果提示Xq21.1存在一种潜在的性别特异性Graves病变异。这可以增加我们对格雷夫斯病背后关键机制的理解，并最终有助于确定可能的治疗靶点。
BackgroundWith several susceptibility single nucleotide polymorphisms identified by case–control association studies, Graves’ disease is one of the most common forms of autoimmune thyroid disease. In this study, we aimed to determine whether any observed differences in genetic associations are influenced by sex in Chinese Han populations.MethodsA total of 8,835 patients with Graves’ disease and 9,936 sex‐matched healthy controls were enrolled in the study. Confirmed by a two‐staged association analysis, sex‐specific analyses among 20 Graves’ disease susceptibility loci were conducted.ResultsA significant sex‐gene interaction was detected primarily at rs5912838 on Xq21.1 between theGPR174andITM2Agenes, whereby male Graves’ disease patients possessed a significantly higher frequency of risk alleles than their female counterparts. Interestingly, compared to women, male patients with Graves’ disease had a higher cumulative genetic risk and higher persistent thyroid stimulating hormone receptor antibody‐positive rate after receiving antithyroid drug therapy for at least 1 year.ConclusionThe findings of this study suggest the existence of one potential sex‐specific Graves’ disease variant on Xq21.1. This could increase our understanding of the pivotal mechanism behind Graves’ disease and ultimately aid in identifying possible therapeutic targets.