Assessment of coronary artery disease severity via non-invasive detection of ABCA1 promoter methylation.

BACKGROUND: ABCA1 is a critical mediator of cholesterol efflux, and hypermethylation of its promoter may lead to transcriptional silencing. However, the relationship between ABCA1 promoter methylation and the severity of coronary artery disease (CAD) remains poorly understood. This study aimed to explore whether ABCA1 promoter methylation correlates with CAD severity and whether it could be used as a non-invasive epigenetic biomarker for auxiliary risk evaluation. METHODS: This case-control study enrolled 80 consecutive patients with CAD (confirmed by coronary angiography) and 80 healthy controls from January 2025 to January 2026. ABCA1 promoter methylation level was quantified using quantitative methylation-specific PCR. Associations with CAD diagnosis, Gensini scores, and clinical parameters were examined, with subgroup analyses by sex and age. RESULTS: ABCA1 methylation levels were significantly elevated in the patients with CAD compared with the controls [median (IQR): 14.01% (8.11-19.28) vs. 9.99% (5.91-13.45), P < 0.05]. Logistic regression revealed that hypermethylation was an independent epigenetic correlate of CAD (OR = 1.087 per 1% increase, 95% CI: 1.010-1.170). This multivariable model was fully adjusted for age, sex, BMI, and serum lipid profile [total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein A, and apolipoprotein B (ApoB)]. Among the patients with CAD, methylation level positively correlated with Gensini score (rs  = 0.311, P < 0.05), TC (rs  = 0.294, P < 0.05), LDL-C (rs  = 0.284, P < 0.05), and ApoB (rs  = 0.365, P < 0.01). In the overall cohort, methylation also correlated with ApoB (rs  = 0.249, P < 0.05), age (rs  = 0.297, P < 0.01), and female sex (rs  = 0.803, P < 0.05). CONCLUSIONS: Peripheral blood ABCA1 promoter methylation shows preliminary potential as a non-invasive epigenetic biomarker to assist auxiliary evaluation of coronary lesion severity, with particular promise in younger adults and women.