ASSOCIATION OF ATG5 GENE POLYMORPHISM WITH ACUTE CORONARY SYNDROME - OBSERVATIONAL STUDY

Abstract

Autophagy, regulated by autophagy-related genes, plays a critical role in cardiomyocyte survival during ischaemic injury and in atherosclerotic plaque stability. Autophagy-related 5 (ATG5) is essential for the ATG12–ATG5–ATG16L1 conjugation system, and polymorphisms in this gene may modulate susceptibility to ACS, although Indian data are limited. We conducted a prospective cross-sectional study of 85 adults with ACS at a tertiary care centre in Karnataka, India, from March 2024 to December 2025. Clinical, biochemical, electrocardiographic, echocardiographic data was recorded. Genomic DNA was extracted from peripheral blood; the ATG5 gene promoter region (NC_000006.12, g.106326240–106326809) was amplified by polymerase chain reaction and analysed by Sanger sequencing. Patients were categorized as ATG5 polymorphism present or absent and the groups were compared. The mean age was 63.40 ± 13.45 years, with 64.7% males. ST-segment elevation myocardial infarction was diagnosed in 52 patients and non-ST-segment elevation myocardial infarction in 33. The ATG5 rs506027 (g.106326589 G>A) polymorphism was detected in 22 of 85 patients (25.9%) — 9 homozygous and 13 heterozygous. Patients with polymorphism had significantly higher triglycerides (182.4 ± 44.8 vs 154.2 ± 36.8 mg/dL, p = 0.004) and low-density lipoprotein cholesterol (158.1 ± 19.8 vs 141.5 ± 32.8 mg/dL, p = 0.028. Left ventricular ejection fraction, major adverse cardiac events and mortality were compared between groups. The ATG5 rs506027 polymorphism was identified in 25.9% of Indian ACS patients and was associated with an adverse lipid profile, suggesting a possible link between altered autophagy and dyslipidaemia in ACS. Larger multi-centric studies with functional validation are needed to define its prognostic and therapeutic relevance.