L型钙离子通道介导的线粒体凋亡途径相关基因甲基化和SNP共调控在碘致自身免疫性甲状腺炎中的作用研究

自身免疫性甲状腺炎(AIT)是一种常见的自身免疫性甲状腺疾病，是环境与遗传因素共同导致的，近年研究表明，碘过量能够导致AIT发病率增加，细胞凋亡是AIT患者甲状腺细胞破坏的主要机制。我们前期研究发现，AIT病例组与对照组线粒体凋亡信号途径及L型钙离子通道的某些基因DNA甲基化有一定的差异。本课题拟在不同碘水平地区进行病例对照研究，研究L型钙离子通道调控的线粒体凋亡信号途径相关基因甲基化及SNP对碘致AIT发生的贡献，并进一步分析甲基化与SNP的共调控作用。在此基础上，通过复制碘致实验性自身免疫性甲状腺炎(EAT)大鼠动物模型，并且在细胞实验中采用L型钙离子通道激动剂和拮抗剂的方法，探讨L型钙离子通道调控的线粒体凋亡信号途径相关基因甲基化在AIT发生中的作用及可能的机制。本研究将促进对碘致AIT发病机制的认识，对于预防碘过量危害具有重要意义，还可指导疾病的分子诊断、开发新的治疗手段。

Autoimmune thyroiditis (AIT) is a common autoimmune thyroid disease, which is caused by both environmental and genetic factors. Recent studies have shown that excessive iodine can increase the incidence of AIT, and apoptosis process is the main mechanism of thyroid cell destruction in patients with AIT. Our previous study found that there were some differences in DNA methylation between mitochondrial apoptosis signaling pathway and L-type calcium channel related genes in the case-control study of AIT. In this study, case-control studies will be conducted in areas with different iodine levels to explore the related genes methylation and SNP of mitochondrial apoptosis signaling pathway regulated by L-type calcium ion channels, and to evaluate their contribution to iodine-induced AIT, and to analyze the co-regulation effect of methylation and SNP. In this study, the potential role and mechanism of related genes methylation of mitochondrial apoptosis signaling pathway regulated by L-type calcium ion channels will be explored by replicating iodine-induced experimental autoimmune thyroiditis (EAT) model in rats and by using agonists and antagonists in cell experiment. This study will promote the understanding of the pathogenesis of iodine-induced AIT, guide the molecular diagnosis of diseases, and develop new therapeutic methods, which are of great significance for the prevention of the harm caused by iodine excess.