目的 探讨三磷酸腺苷结合盒转运蛋白A1(ABCA1)DNA启动子甲基化水平与早发急性冠脉综合征(pACS)及其病变严重程度的关系。方法 收集武警特色医学中心心内科2019年5－12月住院的90例早发急性冠脉综合征患者为pACS组,选取同期本院体检中心的88名健康体检者为对照组。使用焦磷酸测序法测定两组外周血ABCA1 DNA甲基化水平,比较两组血脂、血糖等生化指标及血清炎症标记物的浓度,并采用logistic回归分析影响pACS发病的危险因素。结果 pACS组体重指数(BMI)、糖化血红蛋白(HbA1c)、低密度脂蛋白(LDL)、腰围、平均ABCA1 DNA甲基化水平以及炎症标记物白介素-1β(IL-1β)、C反应蛋白(CRP)和中性粒细胞胞外核酸网循环标志物(cfDNA/NETs)均高于对照组(P<0.05),而高密度脂蛋白(HDL-C)水平及ABCA1蛋白含量低于对照组(P<0.05)。Logistic回归分析发现,ABCA1 DNA甲基化水平(OR=7.413,95%CI:2.070~26.554)、HbA1c(OR=3.646,95%CI:1.008~13.182)、LDL(OR=15.690,95%CI:1.123~69.233)、cfDNA/NETs(OR=1.892,95%CI:1.374~2.604)及IL-1β(OR=1.177,95%CI:1.011~1.370)是pACS发生的独立危险因素,而HDL-C(OR=0.107,95%CI:0.025~0.398)是pACS的保护性因素。此外,研究表明ABCA1 DNA甲基化水平与pACS患者冠脉Gensini评分呈正相关(r=0.648,P<0.001)。结论 ABCA1 DNA启动子甲基化水平是pACS发生的独立危险因素且与冠脉病变程度有关。因此,血清ABCA1-A启动子甲基化水平或许可以作为预测pACS发生风险的生物标志物而被临床应用。
Abstract
Objective To investigates the relationship between ATP binding cassette transporter A1 (ABCA1) DNA methylation level and the risk and severity of premature acute coronary syndrome (pACS). Methods A total of 90 patients with pACS admitted to the Cardiology Department of Characteristics Medical Center of Chinese People’s Armed Police Force from May to December 2019 were selected as pACS group, and 88 healthy physical examinees from the health examination center were selected as control group. Pyrosequencing method was used to determine ABCA1 DNA methylation level in peripheral blood of the two groups, and the biochemical indicators such as blood lipids and blood glucose, as well as the concentration of serum inflammatory markers were compared. Logistic regression was used to analyze the risk factors affecting the onset of pACS. Results The BMI, HbA1c, LDL, waist circumference, average ABCA1 DNA methylation level, and inflammatory markers including interleukin-1 (IL-1β), C-reactive protein (CRP) and circulating free DNA/Neutrophil extracellular traps (cfDNA/NETs) in the pACS group were higher than those in the control group (all P<0.05), while the HDL-C level and ABCA1 protein level were lower than those in the control group (all P<0.05). Further logistic regression analysis revealed that ABCA1 DNA methylation level (OR=7.413, 95%CI: 2.070-26.554), HbA1c (OR=3.646, 95%CI: 1.008-13.182), LDL (OR=15.690, 95%CI: 1.123~69.233), cfDNA/NETs (OR=1.892, 95%CI: 1.374-2.604) and IL-1 β (OR=1.177, 95%CI: 1.011-1.370) were independent risk factors for pACS, while HDL (OR=0.107,95%CI:0.025-0.398) was a protective factor for pACS. In addition, studies showed a positive correlation between ABCA1 DNA methylation level and coronary Gensini scores in pACS patients (r=0.648, P<0.001). Conclusions The methylation level of ABCA1 DNA promoter is an independent risk factor for the occurrence of pACS and is related to the degree of coronary artery disease. Therefore, serum ABCA1-A promoter methylation level may be used as a biomarker to predict the risk of pACS.
关键词
三磷酸腺苷结合盒转运蛋白A1 /
DNA甲基化 /
早发急性冠脉综合征 /
高密度脂蛋白胆固醇 /
Gensini评分
Key words
ATP binding cassette transporter A1 /
DNA methylation /
pACS /
high-density lipoprotein cholesterol /
Gensini score
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基金
天津市救援医学临床研究中心子课题/天津市科技计划项目(15ZXLCSY00040)
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