目的探讨动脉粥样硬化(AS)患者血中三磷酸腺苷结合盒运转体A1(ABCA1)DNA甲基化水平与AS的发生、发展及血脂变化的关系。方法用颈动脉多普勒超声对患者检查、用全自动生化分析仪检测患者血脂水平,以确诊AS患者;收集AS组及正常对照组外周血标本各30例,以荧光定量PCR检测2组的ABCA1 mRNA表达,采用巢式降落式甲基化特异性PCR(nMS-PCR)法检测其ABCA1 DNA甲基化水平,并分析其与血脂水平相关性。结果与正常组相比,AS组甘油三酯(TG)含量升高2.17倍(P〈0.01),胆固醇(CHOL)含量升高1.21倍(P〈0.05),高密度脂蛋白(HDL)升高0.83倍,低密度脂蛋白(LDL)升高1.18倍(P〈0.05);与正常对照组相比,AS组患者ABCA1 mRNA水平降低了63.3%(P〈0.01),ABCA1 DNA甲基化水平,AS组较正常对照组升高了1.38倍(P〈0.01);血脂水平与ABCA1 DNA甲基化水平呈正相关(r=0.489 8,P〈0.01)。结论外周血中ABCA1 DNA高甲基化与AS的发生、发展密切相关。
Objective To analysiz the relationship among DNA methylation level of ATP binding cassette transporter A1(ABCA1) and atherosclerosis occurrence,development and changes of blood lipids.Methods The atherosclerosis patients were confirmed by carotid artery Doppler ultrasound and the serum lipids were measured by ADVIA 2400 Automatic Biochemistry Analyzer.Thirty cases serum of atherosclerosis patients(AS group) and healthy people(control group) were collected,and then DNA was extracted.Fluorescence quantitative PCR were used to detect the mRNA expression of ABCA1.The methylation status changes of ABCA1 were detected by nMS-PCR.And the correlation of DNA methylation levels and blood lipid level was analyzed.Results Serum lipids were detected by automatic biochemical analyzer,and compared with normal group,the TG content of AS group increased 2.17 times(P 0.01),CHOL levels increased 1.21 times(P 0.05),HDL increased 0.83 folds,LDL increased 1.18 times(P 0.05).Besids,compared with the normal control group,the ABCA1 mRNA levels of AS patients decreased by 63.3%(P 0.01),and the ABCA1 DNA methylation level in AS group increased by 1.38 times(P 0.01).And the correction analysis showed that lipid levels and ABCA1 DNA methylation levels were positively correlated(r = 0.489 8,P 0.01).Conclusion The ABCA1 DNA hypermethylation is closely related to the occurrence and development of atherosclerosis.