DNA N6-methyladenine and ABCA1 methylation associations with subclinical coronary atherosclerosis in people with HIV

ABCA1 methylation and N⁶-methyladenine DNA have been identified as epigenetic markers in coronary artery disease. We performed a cross-sectional exploratory study to analyze whether global DNA methylation and ABCA1 promoter methylation in monocytes are associated with coronary atherosclerosis in asymptomatic HIV individuals without cardiovascular disease. Coronary atherosclerosis was defined as a coronary plaque in at least one coronary segment. We included 27 individuals, 15 of whom had coronary atherosclerosis. ABCA1 DNA methylation was higher in participants with coronary atherosclerosis, with statistically significant differences at specific loci related to the activator protein-2 (AP-2) binding site. There were no differences in global levels of 5-methylcytosine and N⁶-methyladenine DNA between individuals with or without coronary atherosclerosis. ABCA1 methylation showed moderate correlations with both the Leaman score and coronary plaque volume, whereas global DNA N⁶-methyladenine had a negative moderate correlation with the segment severity score and LDL cholesterol. Among participants with coronary atherosclerosis, we found a strong negative correlation between ABCA1 methylation and total atheroma plaque volume, with certain loci (CpG 9 and 12) exhibiting very strong associations.