Page 160 - EJMO-9-2

Eurasian Journal of Medicine

and Oncology

ORIGINAL RESEARCH ARTICLE
Identification of potential drug targets for

coronary atherosclerosis from genetic insights:
A Mendelian randomization study

3
Yue Wang 1 , Li-Ming Yan 2 , Tao Wang 1 , and Zhi-Na Liu *
1 Department of Neurology, The Affiliated Hospital of Yan’an University, Yan’an, Shaanxi, China
2 Department of Gynecology, The Affiliated Hospital of Yan’an University, Yan’an, Shaanxi, China
3 Department of Anesthesiology, The Affiliated Hospital of Yan’an University, Yan’an, Shaanxi, China

Abstract

Coronary atherosclerosis (CA) is a chronic cardiovascular disease characterized by
the accumulation of lipid plaques in coronary arteries, leading to vascular narrowing
and impaired myocardial blood supply, which can result in severe complications,
such as angina and myocardial infarction, and may even be life-threatening. Despite
advancements in CA treatment, including medication and surgery, the complex
mechanisms of plaque formation result in some patients responding poorly to existing
*Corresponding author:
Zhi-Na Liu therapies, and specific targets for precision treatment remain unclear. The present
(liuzhina@yau.edu.cn) study utilized Mendelian randomization (MR) to investigate therapeutic targets for
Citation: Wang Y, Yan L, CA. Cis-expression quantitative trait loci (cis-eQTL, exposure data) were obtained from
Wang T, Liu Z. Identification of the eQTLGen consortium, which includes a sample of 31,684 individuals. Summary
potential drug targets for coronary statistics for CA (outcome data) were obtained from the largest CA genome-wide
atherosclerosis from genetic
insights: A Mendelian randomization association studies dataset, covering 456,348 individuals (including 16,041 cases and
study. Eurasian J Med Oncol. 440,307 controls), supplemented with data from the UK Biobank and FinnGen studies
2025;9(2):152-167. for external validation. Colocalization analysis was employed to examine whether CA
doi: 10.36922/ejmo.7387 risk and gene expression were driven by a shared single nucleotide polymorphism,
Received: December 12, 2024 thereby determining colocalized signals. Subsequently, drug prediction and
1st revised: February 6, 2025 molecular docking analysis were conducted to validate the druggability and
pharmacological potential of the target genes, identifying promising therapeutic
2nd revised: February 21, 2025 targets. The MR analysis identified nine drug targets, four of which were supported
3rd revised: March 1, 2025 by colocalization, providing further evidence of their significance. Phenome-wide
Accepted: March 4, 2025 association studies analysis displayed no significant association between the DHX36
gene and other phenotypes. These genes potentially regulate CA by influencing
Published online: April 4, 2025 specific metabolite levels. Molecular docking results indicated good binding affinity
Copyright: © 2025 Author(s). between multiple candidate drugs and proteins encoded by the target genes. Our
This is an Open-Access article study identified nine potential drug targets associated with CA, with four targets
distributed under the terms of the
Creative Commons Attribution further supported for reliability. Given the roles of these genes in inflammation and
License, permitting distribution, metabolic regulation, drug development targeting these genes holds significant
and reproduction in any medium, clinical potential. This study provides genetic evidence supporting the potential
provided the original work is
properly cited. therapeutic benefits of targeting four druggable genes for CA treatment, which will
aid in the development of CA drugs.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Coronary atherosclerosis; drug targets; Mendelian randomization
affiliations.

Volume 9 Issue 2 (2025) 152 doi: 10.36922/ejmo.7387