Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus

Abstract 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....

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Main Authors: Hajer Foddha, Ikram Ben Jeddou, Hana Saoud, Saoussen Chouchene, Abdelhak Foddha, Besma Bel Haj Jrad, Hassen Ben Abdennabi, Amel Haj Khelil
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-07785-x
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Summary:Abstract 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.
ISSN:2045-2322