Abstract
BackgroundATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. Increased ABCA1 promoter methylation level may result in the progression of coronary artery disease. Thus, the present study investigated the association between promoter methylation status of ABCA1 and inflammation in the development of premature coronary artery disease (pCAD).MethodsPCAD patients and healthy individuals (n = 90 each) were recruited from the Characteristic Medical Center of the Chinese People's Armed Police Force from June to December 2019. Using pyrosequencing, the levels of ABCA1 promoter methylation in their blood samples were evaluated. Serum concentrations of lipids, interleukin 1β (IL-1β), C-reactive protein (CRP), and circulating free DNA/Neutrophil extracellular traps (cfDNA/NETs) were also routinely measured and compared between the two groups. P values < 0.05 were considered statistically significant.ResultsThe mean ABCA1 promoter methylation levels were significantly higher in the pCAD group than in the control group (44.24% ± 3.66 vs. 36.05% ± 2.99, P < 0.001). Based on binary logistic regression analysis, ABCA1 promoter methylation level was identified as an independent risk factor for pCAD development (odds ratio = 2.878, 95% confidence interval: 1.802–4.594, P < 0.001). Furthermore, ABCA1 promoter methylation levels were negatively correlated with HDL levels (r = − 0.488, P < 0.001) and positively correlated with the levels of CRP, cfDNA/NETs, and IL-1β (r = 0.389, 0.404, 0.385, respectively; P < 0.001). Multiple regression analysis showed that the serum levels of CRP, IL-1β, and cfDNA/NETs independently affect ABCA1 promoter methylation.ConclusionsOur findings indicate that high methylation levels at the ABCA1 promoter are associated with low HDL cholesterol levels and an increased risk of pCAD. Inflammatory factors and NETs may be involved in the progression of pCAD by affecting ABCA1 promoter methylation levels.
Highlights
ATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects
Our results showed that the DNA methylation levels of eight CpGs and the mean methylation levels of the promoter region of ABCA1-A were significantly higher in the premature coronary artery disease (pCAD) group (P < 0.001), whereas the serum ABCA1 concentration was lower in the pCAD group than that in the control group (Table 3); and there was no correlation between the methylation
Upon considering the study group as the dependent variable and age, sex, body mass index (BMI), waist circumference, TG, total cholesterol (TC), HDLC, Low-density lipoprotein (LDL)-C, HbA1c, diabetes, hypertension, and ABCA1 promoter methylation status as the covariates, we identified the methylation level of the ABCA1 promoter (odds ratio (OR) = 2.878, 95% confidence interval (CI) 1.802– 4.594; P < 0.001), high-density lipoprotein cholesterol (HDL-C) (OR = 0.015, 95% CI 0.004– 0.032; P < 0.001), BMI (OR = 1.892, 95% CI 1.374–2.604; P = 0.017) and HbA1c (OR = 3.162, 95% CI 1.148–8.709; P = 0.026) as independent risk factors for pCAD development (Table 4)
Summary
ATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. The ATP-binding cassette transporter A1 (ABCA1) is an integral membrane protein belonging to the ATP-binding cassette membrane transporter family, and the human ABCA1 gene is located on chr9q31, having a total length of 149 kb and including 50 exons and 49 introns [10]. It mediates cholesterol transfer from the periphery to the liver and intestine in a process called reverse cholesterol transport (RCT), which is critical in promoting the synthesis of high-density lipoproteins (HDLs) and maintaining cholesterol homeostasis and delaying the progression of atherosclerosis (AS)[11]
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