Graduate School, Tianjin Medical University, Tianjin, 300070, China.
Department of Military General Medicine, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, 300162, China.
BMC Cardiovasc Disord. 2021 Feb 8;21(1):78. doi: 10.1186/s12872-021-01894-x.
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).
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.
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.
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.
三磷酸腺苷结合盒转运体 A1（ABCA1）在高密度脂蛋白（HDL）代谢和胆固醇逆转运（RCT）中发挥重要作用，并具有抗炎作用。ABCA1 启动子甲基化水平的增加可能导致冠状动脉疾病的进展。因此，本研究探讨了 ABCA1 启动子甲基化状态与炎症在早发冠心病（pCAD）发展中的关系。
2019 年 6 月至 12 月，从中国人民武装警察部队特色医学中心特征医学中心招募 pCAD 患者和健康个体（各 90 例）。使用焦磷酸测序法评估其血液样本中 ABCA1 启动子甲基化水平。还常规测量并比较了两组患者的血脂、白细胞介素 1β（IL-1β）、C 反应蛋白（CRP）和循环游离 DNA/中性粒细胞胞外陷阱（cfDNA/NETs）浓度。P 值<0.05 被认为具有统计学意义。
pCAD 组的 ABCA1 启动子甲基化水平明显高于对照组（44.24%±3.66 对 36.05%±2.99，P<0.001）。基于二元逻辑回归分析，ABCA1 启动子甲基化水平被确定为 pCAD 发展的独立危险因素（比值比=2.878，95%置信区间：1.802-4.594，P<0.001）。此外，ABCA1 启动子甲基化水平与 HDL 水平呈负相关（r=-0.488，P<0.001），与 CRP、cfDNA/NETs 和 IL-1β水平呈正相关（r=0.389、0.404、0.385，分别；P<0.001）。多元回归分析显示，血清 CRP、IL-1β 和 cfDNA/NETs 水平独立影响 ABCA1 启动子甲基化。
我们的研究结果表明，ABCA1 启动子的高甲基化水平与低 HDL 胆固醇水平和 pCAD 风险增加有关。炎症因子和 NETs 可能通过影响 ABCA1 启动子甲基化水平而参与 pCAD 的进展。
