Wang Di, Liu WenHui, Wang LiLi, Zhang Ning, Huang XiaoFeng, Chen HuoYing
Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China.
Guilin Medical University, Guilin, 541199, China.
BMC Cardiovasc Disord. 2025 May 24;25(1):397. doi: 10.1186/s12872-025-04860-z.
Coronary atherosclerosis narrows or occludes blood vessels, resulting in myocardial ischemia and hypoxia, which ultimately leads to coronary heart disease (CHD). The pathogenesis of CHD remains insufficiently elucidated. A widely accepted hypothesis is that various stimuli induce arterial intima injury, and atherosclerosis (AS)formation reflects the inflammatory-fibroproliferative response of the intima to such injury. Milk fat globule epidermal growth factor 8 (MFG-E8) is expressed in cells implicated in CHD development, including macrophages, endothelial cells, and vascular smooth muscle cells, suggestion it play a regulatory role in multiple key stages of AS progression (such as foam cell formation and plaque instability). However, theassociation between MFG-E8 gene polymorphisms and CHD susceptibility in humans remains unclear. This study aimed to investigate the relationship between serum MFG-E8 levels, MFG-E8 single nucleotide polymorphisms (SNPs), and CHD. Additionally, We genotyped tag SNPs to provide insights for future screening of high-risk CHD populations and the identification of novel therapeutic targets.The serum MFG-E8 concentration was significantly lower in the CHD group(n = 158) than in the control group (n = 183) (P < 0.001). The rs1878326 polymorphism showed no statistically significant association with CHD susceptibility (P > 0.05). The rs4945† (C > A, reverse complement equivalent to NCBI G > T) polymorphism in the MFG-E8 gene was associated with an increased risk of CHD (CA genotype vs.CC genotype: OR = 2.029, 95% CI: 1.229-3.349, P = 0.006; A allele vs. C allele: OR = 1.835, 95% CI: 1.153-2.921, P = 0.010). However, the rs4945 polymorphism did not significantly influence serum MFG-E8 levels. Our findings suggest that the CA genotype and A allele of the MFG-E8 rs4945 polymorphism are associated with an elevated CHD risk in a Chinese Han population. However, due to the limited sample size of the study, further studies are needed to validate these associations between MFG-E8 gene polymorphisms and CHD susceptibility.
冠状动脉粥样硬化会使血管变窄或堵塞，导致心肌缺血和缺氧，最终引发冠心病（CHD）。冠心病的发病机制仍未得到充分阐明。一个被广泛接受的假说是，各种刺激会导致动脉内膜损伤，而动脉粥样硬化（AS）的形成反映了内膜对这种损伤的炎症-纤维增殖反应。乳脂肪球表皮生长因子8（MFG-E8）在参与冠心病发展的细胞中表达，包括巨噬细胞、内皮细胞和血管平滑肌细胞，这表明它在AS进展的多个关键阶段（如泡沫细胞形成和斑块不稳定）发挥调节作用。然而，MFG-E8基因多态性与人类冠心病易感性之间的关联仍不清楚。本研究旨在探讨血清MFG-E8水平、MFG-E8单核苷酸多态性（SNP）与冠心病之间的关系。此外，我们对标签SNP进行基因分型，为未来筛查冠心病高危人群和确定新的治疗靶点提供见解。冠心病组（n = 158）的血清MFG-E8浓度显著低于对照组（n = 183）（P < 0.001）。rs1878326多态性与冠心病易感性无统计学显著关联（P > 0.05）。MFG-E8基因中的rs4945†（C > A，反向互补相当于NCBI中的G > T）多态性与冠心病风险增加相关（CA基因型与CC基因型：OR = 2.029，95% CI：1.229 - 3.349，P = 0.006；A等位基因与C等位基因：OR = 1.835，95% CI：1.153 - 2.921，P = 0.010）。然而，rs4945多态性并未显著影响血清MFG-E8水平。我们的研究结果表明，MFG-E8 rs4945多态性的CA基因型和A等位基因与中国汉族人群冠心病风险升高相关。然而，由于本研究样本量有限，需要进一步研究来验证MFG-E8基因多态性与冠心病易感性之间的这些关联。
