The impact of immunity on the risk of coronary artery disease: insights from a multiomics study.

IF 3.6 4区医学 Q1 MEDICINE, GENERAL & INTERNAL Postgraduate Medical Journal Pub Date : 2024-08-24 DOI:10.1093/postmj/qgae105

Rutao Bian, Dongyu Li, Xuegong Xu, Li Zhang

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Abstract

Background: 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.

Methodology: 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.

Results: 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.

Conclusion: 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.

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免疫力对冠心病风险的影响：一项多组学研究的启示。

背景：免疫炎症与冠状动脉疾病（CAD）的进展密切相关，因此有必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）与冠状动脉疾病和心肌梗塞（MI）之间的因果关系，发现这些疾病的潜在治疗靶点：我们进行了基于汇总数据的孟德尔随机分析，以评估与CAD和MI相关的RIRGs表达定量性状位点和甲基化定量性状位点的治疗靶点。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：结果：通过多组学整合，我们将 EIF2B2、FCHO1 和 DDT 确定为 CAD 风险基因。值得注意的是，EIF2B2 和 FCHO1 与心肌梗死有显著关联。EIF2B2 的高表达受 cg16144293 的调节，rs175438 会增加患 CAD 和 MI 的风险。相反，受 cg18329931 调节的 FCHO1 表达增强则降低了 rs13382133 的 CAD 和 MI 风险。受 cg11060661 和 cg09664220 影响的 DDT 上调与 rs5760120 的 CAD 风险降低有关。共定位分析确定了这些关系：结论：EIF2B2、FCHO1 和 DDT 代表了 RIRGs 中 CAD 进展的风险位点。我们对这些基因的鉴定加深了对 CAD 发病机制的了解，并指导了未来的药物开发工作。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Postgraduate Medical Journal 医学-医学：内科

CiteScore

8.50

自引率

2.00%

发文量

131

审稿时长

2.5 months

期刊介绍： Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.