硒蛋白P参与甲状腺过氧化物酶抗体发生及硒治疗效果的作用机制研究

项目名称： 硒蛋白P参与甲状腺过氧化物酶抗体发生及硒治疗效果的作用机制研究

项目编号： No.81200571

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 毛金媛

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 硒与甲状腺结构和功能密切相关，在体内主要通过硒蛋白发挥作用，多项RCT研究和荟萃分析显示补硒治疗可显著降低甲状腺过氧化物酶抗体（TPOAb）滴度，但存在个体差异。本研究拟探讨硒蛋白P（SEPP1）的基因型和蛋白表型对TPOAb阳性发生和补硒前后滴度变化的影响及作用机制。人群研究：将对SEPP1基因3'非翻译区的SNP rs7579基因分型、检测血浆SEPP1总蛋白浓度和60KD亚型比例，观察它们与TPOAb及补硒效果的相关性。体外实验：将初步探讨microRNA对SEPP1表达的调控作用，通过基因重组技术构建含有rs7579不同等位基因的荧光素酶报告载体和SEPP1表达载体，观察功能性SNP rs7579 G/A等位基因是否影响miR-202-3p与靶基因结合，并最终影响SEPP1蛋白表型。本研究将有助于揭示自身免疫甲状腺病的发病机制，为预测TPOAb阳性患者补硒治疗效果提供分子生物学依据

中文关键词： 甲状腺过氧化物酶抗体；硒；硒蛋白P；单核苷酸多态性；微小RNA

英文摘要： Selenium has substantial structural and functional role in thyroid. Its biological functions are displayed by incorporating into selenoprotein. Several RCT studies and meta-analysis shows that selenium supplementation is associated with a significant decrease in TPOAb titers, but the treatment effects are featured with individual difference. This reseach is to explore the effect and molecular mechanism of selenoprotein P (SEPP1) genotype and protein phenotype on the TPOAb titers before and after selenium treatment. In population-based study, SNP rs7579 in 3'-untranslated region of SEPP1 gene will be genotyped and plasma SEPP1 concentration and percentage of 60KD subtype detected, in order to analysize the association between SEPP1, TPOAb titers and the effect of selenium treatment. In in vitro study, luciferase reporter plasmid and SEPP1 expression plasmid will be constructed using gene recombination techenology. The binding of miR-202-3p and target gene will be measured by lucifurase assays and SEPP1 expression by western blot. These experiments will determine whether microRNA regulates SEPP1 expression depending on G/A allele of functional SNP rs7579, finally resulting in SEPP1 protein phenotype change. This research will be contributed to uncover the pathogenesis of autoimmune thyroid diseases and provide th

英文关键词： TPOAb；Selenium；SEPP1；SNP；microRNA