Foddha Hajer, Ben Jeddou Ikram, Saoud Hana, Chouchene Saoussen, Foddha Abdelhak, Bel Haj Jrad Besma, Ben Abdennabi Hassen, Haj Khelil Amel
Laboratory of human genome and multifactorial diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, BP N° 74, Street Tahar Haddad, Monastir, 5000, Tunisia.
Laboratory of Genetics, Biodiversity and Bioresource Valorization (LR11ES41), Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia.
Sci Rep. 2025 Jul 1;15(1):21104. doi: 10.1038/s41598-025-07785-x.
Coronary artery disease (CAD) is a major global health burden influenced by genetic and environmental factors. Polymorphisms in the CCL5 gene, which regulates inflammatory responses, have been linked to CAD susceptibility and severity. This study examined the association of -403G/A and In1.1T/C polymorphisms in the CCL5 gene with CAD risk and severity, focusing on the role of diabetes mellitus (DM). A case-control study included 480 participants: 240 CAD patients (122 with DM and 118 without DM) and 240 healthy controls. CAD diagnosis was confirmed via coronary angiography, and severity was assessed using the Gensini score. Genotyping of -403G/A (rs2107538) and In1.1T/C (rs2280789) polymorphisms was performed using PCR-RFLP. TheA allele of -403G/A SNP was significantly associated with CAD susceptibility (p = 0.03; OR = 1.37, 95% CI: 1.03-1.82) and remained significant after adjusting for confounders. While In1.1T/C was not associated with overall CAD risk, the CC genotype correlated with higher Gensini scores, indicating greater severity (p < 0.05). Subgroup analysis showed a significant association between the C allele of In1.1T/C and CAD in diabetic patients (p = 0.009; OR = 2.06, 95% CI: 1.18-3.61) but not in non-diabetic patients. DM also strengthened the link between - 403G/A and CAD severity. These findings suggest that CCL5polymorphisms influence CAD risk and severity, with DM acting as a modifier, offering insights for personalized CAD management in diabetic populations.
冠状动脉疾病（CAD）是一种受遗传和环境因素影响的主要全球健康负担。调节炎症反应的CCL5基因多态性与CAD易感性和严重程度有关。本研究检测了CCL5基因-403G/A和In1.1T/C多态性与CAD风险和严重程度的关联，重点关注糖尿病（DM）的作用。一项病例对照研究纳入了480名参与者：240例CAD患者（122例患有DM，118例未患有DM）和240名健康对照者。通过冠状动脉造影确诊CAD，并使用Gensini评分评估严重程度。使用PCR-RFLP对-403G/A（rs2107538）和In1.1T/C（rs2280789）多态性进行基因分型。-403G/A单核苷酸多态性的A等位基因与CAD易感性显著相关（p = 0.03；OR = 1.37，95%CI：1.03-1.82），在调整混杂因素后仍具有显著性。虽然In1.1T/C与总体CAD风险无关，但CC基因型与更高的Gensini评分相关，表明严重程度更高（p < 0.05）。亚组分析显示，In1.1T/C的C等位基因与糖尿病患者的CAD之间存在显著关联（p = 0.009；OR = 2.06，95%CI：1.18-3.61），而在非糖尿病患者中则无此关联。DM还加强了-403G/A与CAD严重程度之间的联系。这些发现表明，CCL5多态性影响CAD风险和严重程度，DM起修饰作用，为糖尿病人群CAD的个性化管理提供了见解。
