早发性冠心病的基因学研究进展

早发性冠心病的遗传背景包括单基因罕见突变和多基因常见突变累积冠心病。前者的致病基因主要与脂质代谢、血管内皮完整性及内皮功能、血栓形成有关,其中低密度脂蛋白胆固醇代谢相关基因的作用尤为重要;后者遗传背景的研究与常见的多基因复杂疾病相似,主要通过基因组关联研究、表达数量性状位点分析、多基因风险模型建立等基因组学分析工具进行。此外,近年来兴起的高维组学技术和基因调控网络也为解释多基因发病的早发性冠心病的遗传背景提供了新的思路和重要技术支持。

Advances in genetic research of premature coronary artery disease

According to the genetic background, premature coronary artery disease (PCAD) can be divided into two categories: PCAD caused by rare mutations of single gene and PCAD caused by accumulation of common mutations of multiple genes. Mendelian forms of PCAD support three major biological pathways, including lipid metabolism, vascular wall integrity and function, and thrombosis. And It highlights the importance of lipid metabolism. The research of the latter is similar to that of common polygenic complex diseases. The risk stratification of patients is mainly conducted by polygenic risk score in genome-wide association studies. Furthermore, the development of high-dimensional omics technologies and gene regulation networks (GRNs) also provide new ideas and important technical support for the interpretation of the genetic background of polygenic PCAD.