既往研究表明下调MIA3基因促进单核细胞黏附和迁移。新近全基因组关联分析（GWAS）发现MIA3是冠心病新的致病基因，但在冠心病发生、发展过程中具体致病分子机制尚不清楚。我们前期研究发现MIA3基因3'-非编码区存在一个功能性遗传变异,引起microRNA-3187-3p（miR-3187-3p）结合，下调MIA3基因表达，并与冠心病发生及病变程度相关联。基于MIA3基因功能和前期研究结果，我们假设miR-3187-3p通过与MIA3基因3'-非编码区功能性遗传变异相结合，下调MIA3基因表达, 促进单核细胞向内皮细胞的黏附和迁移，加重动脉粥样斑块形成。为了验证这一假说，我们将综合运用冠心病病例-对照随访人群，MIA3和APOE基因敲除小鼠，细胞黏附和迁移实验，双报告基因，以及生物信息学手段，从人群、动物、细胞和分子水平，系统阐明MI3基因3'-非编码区功能性遗传变异致冠心病的机制。

Previous studies have shown that reduction of MIA3 expression promoted the adhesion and migration of monocytes. Recent genome-wide association study(GWAS) identified MIA3 as a novel candidate gene for coronary heart disease(CHD). However,the potential molecular mechanism involved in CHD remained unknown. Our previous studies have found that there was a functional genetic variant within the 3'-untranslated region(3'-UTR) of MIA3 gene, creating a miR-3187-3p binding site, resulting in down regulation of MIA3 gene expression and was associated with risk and severity of CHD. Based on these discovery, we hypothesized that miR-3187-3p might bind to the 3'UTR of MIA3, resulting in down regulation of MIA3 expression, promoting adhesion and migration of monocytes, increasing the burden of atherosclerosis. To test this hypothesis, we will make a comprehensive study by using a follow up case-control study, MIA3 and APOE knockout mice, cell adhesion and migration experiments, dual reporter gene system, as well as bio-informatics analysis in population, animal,cellular and molecular levels, to systematically determinate potential mechanism of MI3 3'-UTR functional variant involved in CHD.