Fang An1,2, Chao Liu3, Xiujuan Wang4, Tan Li5, Hao Fu2, Buhe Bao6, Hongliang Cong7,8, Jihong Zhao9. 1. Graduate School, Tianjin Medical University, Tianjin, 300070, China. 2. Department of Military General Medicine, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, 300162, China. 3. Institute of Cardiovascular disease, Tianjin Chest Hospital, Tianjin, 300222, China. 4. Institute of Cardiovascular Disease, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, 300162, China. 5. Department of Pathogen Biology, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, China. 6. Department of Clinical Laboratory, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, 300162, China. 7. Institute of Cardiovascular disease, Tianjin Chest Hospital, Tianjin, 300222, China. hongliangcong2020@163.com. 8. Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300222, China. hongliangcong2020@163.com. 9. Department of Military General Medicine, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, 300162, China. zjhwj@126.com.
Abstract
BACKGROUND: 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. 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). METHODS: PCAD 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. RESULTS: The 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. CONCLUSIONS: Our 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.
BACKGROUND: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. 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). METHODS: PCAD 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. RESULTS: The 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. CONCLUSIONS: Our 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.