遗传因素在冠心病的发病机制中具有重要作用。尽管已经有大量的基因被发现和冠心病的发病风险相关，但大部分功能未完全阐明。我们前期的研究中发现AHNAK2基因新的变异105415265A>T和冠心病的发病风险相关，但具体机制不清。文献表明AHNAK2基因参与糖脂代谢紊乱，并级联加剧MAPK信号通路介导的血管内皮损伤与平滑肌增殖，共同促进冠心病的发生发展。AHNAK2基因敲除小鼠也表现为炎症反应激活及血脂代谢紊乱。因此，我们推测AHNAK2基因新变异105415265A>T，可能通过影响炎症及血脂代谢途径，从而参与冠心病的发病机制。为了验证上述假说，本项目拟采用基因编辑技术分别在三种细胞水平、多种动物模型水平进行功能研究。并利用蛋白质科学研究的技术手段，对蛋白相关功能调控进行探讨，揭示其在冠心病发生发展中的作用及其机制，为早期识别易感人群，实现早期个体化的干预奠定理论基础。

Genetic factors play an important role in the pathogenesis of coronary heart disease. Although a large number of genes have been found to be associated with the risk of coronary heart disease, most of their functions have not been fully clarified. In our previous study, we found that the new variation of AHNAK2 gene 105415265A>T was associated with the risk of coronary heart disease, but the specific mechanism was unclear. Literature has shown that AHNAK2 gene is involved in the disorder of glucose and lipid metabolism, and the cascade aggravation of the vascular endothelial injury and the proliferation of smooth muscle mediated by MAPK signaling pathway, which jointly promote the occurrence and development of coronary heart disease. AHNAK2 knockout mice also showed activation of inflammatory response and disorder of blood lipid metabolism.Therefore, we speculated that the new AHNAK2 gene variant 105415265A>T may be involved in the pathogenesis of coronary heart disease by affecting inflammation and blood lipid metabolism pathways. In order to test the above hypothesis, this project intends to use gene editing technology to carry out functional studies at the level of three kinds of cells and a variety of animal models. By using the technical means of protein scientific research to discover the regulation of protein-related functions, to reveal the role and mechanism of protein-related functions in the occurrence and development of coronary heart disease, and to lay a theoretical foundation for early identification of susceptible population and for early individualized intervention.