Bian Rutao, Li Dongyu, Xu Xuegong, Zhang Li
Department of Cardiology, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, Henan 450000, China.
The Affiliated Zhengzhou Hospital of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan 450000, China.
Postgrad Med J. 2024 Dec 23;101(1191):50-59. doi: 10.1093/postmj/qgae105.
Immune inflammation is intricately associated with coronary artery disease (CAD) progression, necessitating the pursuit of more efficacious therapeutic strategies. This study aimed to uncover potential therapeutic targets for CAD and myocardial infarction (MI) by elucidating the causal connection between regulatory immune-related genes (RIRGs) and these disorders.
We performed summary data-based Mendelian randomization analysis to assess the therapeutic targets linked to expression quantitative trait loci and methylation quantitative trait loci of RIRGs in relation to CAD and MI. Independent validation cohorts and datasets from coronary artery and left ventricular heart tissue were analyzed. To strengthen causal inference, colocalization analysis and PhenoScanner phenotype scans were employed.
Utilizing multiomics integration, we pinpointed EIF2B2, FCHO1, and DDT as CAD risk genes. Notably, EIF2B2 and FCHO1 displayed significant associations with MI. High EIF2B2 expression, regulated by cg16144293, heightened CAD and MI risk at rs175438. In contrast, enhanced FCHO1 expression, modulated by cg18329931, reduced CAD and MI risk at rs13382133. DDT upregulation influenced by cg11060661 and cg09664220 was associated with decreased CAD risk at rs5760120. Colocalization analysis firmly established these relationships.
EIF2B2, FCHO1, and DDT represent risk loci for CAD progression within RIRGs. Our identification of these genes enhances understanding of CAD pathogenesis and directs future drug development efforts.
免疫炎症与冠状动脉疾病（CAD）的进展密切相关，因此需要寻求更有效的治疗策略。本研究旨在通过阐明调节性免疫相关基因（RIRGs）与这些疾病之间的因果关系，揭示CAD和心肌梗死（MI）的潜在治疗靶点。
我们进行了基于汇总数据的孟德尔随机化分析，以评估与RIRGs的表达数量性状位点和甲基化数量性状位点相关的治疗靶点与CAD和MI的关系。分析了来自冠状动脉和左心室心脏组织的独立验证队列和数据集。为了加强因果推断，采用了共定位分析和PhenoScanner表型扫描。
利用多组学整合，我们确定EIF2B2、FCHO1和DDT为CAD风险基因。值得注意的是，EIF2B2和FCHO1与MI显示出显著关联。由cg16144293调控的高EIF2B2表达在rs175438处增加了CAD和MI风险。相反，由cg18329931调控的FCHO1表达增强在rs13382133处降低了CAD和MI风险。受cg11060661和cg09664220影响的DDT上调与rs5760120处CAD风险降低相关。共定位分析明确证实了这些关系。
EIF2B2、FCHO1和DDT是RIRGs中CAD进展的风险位点。我们对这些基因的鉴定增进了对CAD发病机制的理解，并指导未来的药物开发工作。
