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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author Hajer Foddha
Ikram Ben Jeddou
Hana Saoud
Saoussen Chouchene
Abdelhak Foddha
Besma Bel Haj Jrad
Hassen Ben Abdennabi
Amel Haj Khelil
author_facet Hajer Foddha
Ikram Ben Jeddou
Hana Saoud
Saoussen Chouchene
Abdelhak Foddha
Besma Bel Haj Jrad
Hassen Ben Abdennabi
Amel Haj Khelil
author_sort Hajer Foddha
collection DOAJ
description 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.
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spelling doaj-art-2512e90badbe411d820c65ec3c4db30d2025-08-20T04:01:23ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-07785-xImpact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitusHajer Foddha0Ikram Ben Jeddou1Hana Saoud2Saoussen Chouchene3Abdelhak Foddha4 Besma Bel Haj Jrad5Hassen Ben Abdennabi 6Amel Haj Khelil 7Laboratory of human genome and multifactorial diseases (LR12ES07), Faculty of Pharmacy, University of MonastirLaboratory of human genome and multifactorial diseases (LR12ES07), Faculty of Pharmacy, University of MonastirLaboratory of Genetics, Biodiversity and Bioresource Valorization (LR11ES41), Higher Institute of Biotechnology of Monastir, University of MonastirLaboratory of human genome and multifactorial diseases (LR12ES07), Faculty of Pharmacy, University of MonastirCardiology Department, FattoumaBourguiba Hospital, University of MonastirLaboratory of Genetics, Biodiversity and Bioresource Valorization (LR11ES41), Higher Institute of Biotechnology of Monastir, University of MonastirLaboratory of human genome and multifactorial diseases (LR12ES07), Faculty of Pharmacy, University of MonastirLaboratory of human genome and multifactorial diseases (LR12ES07), Faculty of Pharmacy, University of MonastirAbstract 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.https://doi.org/10.1038/s41598-025-07785-xCoronary artery diseaseCCL5 gene polymorphismsDiabetes mellitusGenetic susceptibilityGene–environment interactions
spellingShingle Hajer Foddha
Ikram Ben Jeddou
Hana Saoud
Saoussen Chouchene
Abdelhak Foddha
Besma Bel Haj Jrad
Hassen Ben Abdennabi
Amel Haj Khelil
Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
Scientific Reports
Coronary artery disease
CCL5 gene polymorphisms
Diabetes mellitus
Genetic susceptibility
Gene–environment interactions
title Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
title_full Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
title_fullStr Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
title_full_unstemmed Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
title_short Impact of CCL5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
title_sort impact of ccl5 gene polymorphisms on coronary artery disease risk and severity in the context of diabetes mellitus
topic Coronary artery disease
CCL5 gene polymorphisms
Diabetes mellitus
Genetic susceptibility
Gene–environment interactions
url https://doi.org/10.1038/s41598-025-07785-x
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