摘要
目的近期研究发现FOXP3基因CNS2区的去甲基化水平可反映调节性T细胞水平。调节性T细胞在动脉粥样硬化中起保护作用。本研究旨在应用焦磷酸测序的方法检测该基因片段的甲基化水平,评估冠心病患者调节性T细胞水平的变化。方法和结果本研究纳入114位急性冠脉综合征患者以及11位冠脉造影正常者。提取外周血DNA,应用焦磷酸测序的方法检测的FOXP3基因CNS2区域甲基化水平。试验发现,冠心病患者FOXP3基因甲基化分析所得到的调节性T细胞水平均较对照者显著降低(正常对照组11.97%±2.01%,急性冠脉综合征组9.79%±1.77%;P<0.001);分别根据冠脉病变血管的严重程度和Gensini评分的三分位数将冠心病患者分组分析,结果提示各组冠心病患者较正常对照者的调节性T细胞均显著减少。FOXP3-CNS2的去甲基化水平与冠心病的严重程度呈反比(r=-0.206,P<0.05)。在去除传统危险因素的影响后,两者相关性降低,且无显著性差异。结论本研究显示冠心病患者的去甲基化FOXP3所代表的调节性T细胞水平显著降低,调节性T细胞的减少和动脉粥样硬化的严重程度尚需进一步证实。
Objective Demethylation in the DNA that encodes transcription factor forkhead box P3 （FOXP3）-CNS2 is identified as the most specific marker for human Regulatory T （Treg） cells, Treg cells play a protective role in atherosclerosis. We aim to evaluate Treg levels in CAD patients by pyrosequencing based on Treg-specific DNA demethylation within FOXP3 gene. Methods and Results We included 114 acute coronary syndromes （ACS） patients and 11 control subjects with normal coronary artery on angiography （NCA） in our study. DNA from peripheral blood was collected to determine Treg levels by pyrosequencing based DNA methylation analysis. We found that Treg levels, quantified by the demethylation rate of CNS2 in FOXP3 gene were decreased in ACS patients （NCA 11.97% ± 2,01%; ACS 9.79% i 1.77%） as well as each CAD group classified by the number of diseased vessel or Gensini score. This decline was inversely related to the severity ol CAD （r=-0.206, P〈0.05）. After adjustment for traditional risk factors, the association didn＇t remain. Conclusion Our data demonstrate tha＇ Treg cells are decreased in CAD patients. The relationship between FOXP3-CNS2 methylation and the severity of atherosclerosis needs further studt.
作者
贾镭
祝领
王晓建
王继征
孙凯
宋雷
惠汝太
LEI JIA ZHU LING WANG Xiao-jian WANG Ji-Zheng SUN KAIj SONG LEI HUI Ru-tai(Fuwai Hospital ,Chinese Academy of Medical ng Union Medical College, National Center for Cardiovasclur Diseases China, Beijing 100037 China ShanXi Provincial People＇s Hospital epartment of Cardiology, Xi ＇an 710068, China)
出处
《中国分子心脏病学杂志》
CAS
2016年第5期1842-1845,共4页
Molecular Cardiology of China
基金
国家自然科学基金青年基金(81300221)
高等学校博士学科点专项科研基金(20131106120007)
