本课题组前期研究发现：过量碘摄入增加自身免疫甲状腺病（AITD）发病风险。表观遗传学修饰在免疫应答过程中发挥重要作用，环境因素可以改变表观修饰，因此我们提出假说：碘摄入量增加作为环境因素，可以导致表观遗传修饰改变，使AITD相关基因异常表达，诱发和加重AITD。本课题拟采用AITD患病不一致的单卵孪生子(n=60)进行全基因组表观基因组关联研究（EWAS），确定与AITD相关的异常DNA甲基化和组蛋白修饰位点、并在AITD散发病例(n=150)中得到验证；利用过量碘干预NOD-H2h4小鼠AITD模型，研究过量碘对表观修饰的影响；体外过量碘处理甲状腺细胞，研究碘过量改变表观修饰的机制。从而确定“过量碘-表观修饰-自身免疫甲状腺病”三者的关系。研究成果将为我国制定合理的碘营养标准提供循证医学依据，为从表观遗传学水平预防、治疗AITD提供理论基础。

Our previous research found that excess iodine intake induced and promoted the development of Autoimmune thyroid disease(AITD). The epigenetic modulation plays a significant role in autoimmune disorders. Abnormal epigenetic changes can be induced by environmental factors. We hypothesize that: increased iodine intake→epigenetic modification change→the genes associated with AITD obtain altered DNA methylation, histone acetylation/methylation→abnormal expression of AITD related gene , which triggers and aggravates autoimmunity in thyroid. To verify the hypothesis, we designed clinical study that recruit subjects of monozygotic twins (n=60) to localize genes which are differentially modified in AITD patients by techniques of epigenome-wide association study(EWAS). And the result will be confirmed in case-control (n=150). Furthermore, the role of excessive iodine here will be investigated. Experimental researches in vivo and in vitro are designed to explore the mechanism of how excessive iodide changes epigenetic modification and the function of differentially modified genes leads to immune-tolerance loss in the thyroid. The achievement of this study will provide evidence for iodine supplementation policy, moreover, a theoretical foundation for novel prophylactic and therapeutic methods in AITD.