桥本甲状腺炎是自身免疫性甲状腺病(ATD)的一个类型，是原发性甲减最主要的原因。研究发现环境与遗传因素互作的表观遗传学改变可能是ATD重要病因。本课题组发现ATD病例对照组间碘营养状态、Th1/Th2/Th17/Treg细胞比例、CD40、IL2RA等易感基因的启动子区DNA甲基化频率有差异。故假设碘摄入量通过表观遗传途径影响ATD易感基因的表达，影响免疫系统的功能及相关基因表达异常，启动自身免疫反应，促使有遗传背景的个体发病。拟采用蛋白组学技术分析病例对照组间的组蛋白修饰差异，应用ChIP-Seq技术分析病例对照组间组蛋白差异所影响的基因组区域，及其重要基因对外周血Th1、Th2、Th17、Treg细胞亚群比例的影响。研究结果将首次阐述碘摄入量是否通过影响表观遗传修饰改变了疾病的易感性，为寻找ATD发病的表观遗传标志、高危人群的早期防治及科学合理补碘做出努力。

Hashimoto’s thyroiditis（HT） is a type of Autoimmune thyroid diseases(ATD) and is a main reason of primary hypothyroidism. Significant progress has been made in our understanding of the mechanisms leading to ATD, which epigenetics is a molecular link between genes and enviroment fantros.Our studies have found that there were interaction among DNA methylation modifications of susceptibility genes promoter by MeDIP-Seq technology and the proportion of Th1,Th2，Th17,Treg in vitro by Flow cytometry and median urinary iodine in ATD cases and controls. So our hypothesis is that epigenetic changes of ATD susceptibility genes in response to environmental stimulus of iodine intake would contribute to development of ATD in the individual with genetic susceptibility by autoimmune respones unbalance and genes expression abnormality. Based on the above study found, the project will further analyze histone post-translational modifications of ATD susceptibility genes of peripheral blood leukocytes in HT cases and controls by proteomic technologies, and find the genomic regions affected by the difference of histone post-translational modifications between case and control through ChIP-Seq technology targeting specific histone modifications. Molecular biological functional verification tests of important genes of important regions found and their affects on the proportion of Th1、Th2、Th17、Treg cell subsets, will be studied. This perspective will provide some insights into whether iodine intake influnce epigenetic modifications, including DNA methylaiton and histone post-translational modifications, resulting in increased disease susceptibility of individual for first time, which would find epigenetic marker of ATD development and help prevention early and scientific iodine intake of susceptibility individuals .