蛋白S基因启动子区甲基化与蛋白S血浆浓度及肺血栓关系研究
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摘要
目的分析抗凝因子PS、PC和AT基因启动子区甲基化水平及其血浆中的浓度,阐明抗凝因子基因甲基化与肺血栓栓塞症之间的关系。方法焦磷酸测序法检测肺血栓栓塞症组和对照组之间抗凝因子甲基化水平差异;进一步使用ELISA检测高甲基化样本和对照组抗凝因子血浆浓度差异。结果与正常对照组相比,肺血栓栓塞症组中PS基因启动子区甲基化率明显升高(P<0.001);高甲基化样本的PS血浆浓度较对照组明显降低(P=0.0051)。结论 PS因子启动子区甲基化水平升高,导致PS血浆浓度降低,进而促进肺血栓的形成。
Objective To show the relationship between gene methylation of anticoagulation factor and pulmonary thromboembolism by analyzing the promoter methylation level and plasma concentration of anticoagulant factor PS, PC and AT. Methods To detect the promoter methylation level of anticoagulation factor between pulmonary thromboembolism group and control group by pyrosequencing. Further, ELISA was used to detect the difference of plasma concentration of anticoagulant factor between hypermethylation samples and control group. Results Compared with the normal control group, the methylation rate of PS gene promoter in the pulmonary thromboembolism group increased significantly(P<0.001), and the plasma PS concentration in hypermethylation samples was significantly lower than that in the control group(P=0.0051).Conclusion The increase of methylation level in the promoter region of PS gene leads to the decrease of plasma concentration of PS, which promotes the formation of pulmonary thrombosis.
Objective To show the relationship between gene methylation of anticoagulation factor and pulmonary thromboembolism by analyzing the promoter methylation level and plasma concentration of anticoagulant factor PS, PC and AT. Methods To detect the promoter methylation level of anticoagulation factor between pulmonary thromboembolism group and control group by pyrosequencing. Further, ELISA was used to detect the difference of plasma concentration of anticoagulant factor between hypermethylation samples and control group. Results Compared with the normal control group, the methylation rate of PS gene promoter in the pulmonary thromboembolism group increased significantly(P<0.001), and the plasma PS concentration in hypermethylation samples was significantly lower than that in the control group(P=0.0051).Conclusion The increase of methylation level in the promoter region of PS gene leads to the decrease of plasma concentration of PS, which promotes the formation of pulmonary thrombosis.
引文
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[2]Leizorovicz A,Cohen AT,Turpie AG,etal.Randomized,placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients[J].Circulation.2004,110:874-879.
[3]Alikhan R,Cohen AT,Combe S,etal.Prevention of venous thromboembolism in medical patients with enoxaparin:a subgroup analysis of the MEDENOX study[J].Blood coagulation&fibrinolysis:an international journal in haemostasis and thrombosis.2003,14:341-346.
[4]李小鹰,樊瑾,程友琴,等.老年急症内科住院病人静脉血栓栓塞的患病率高但预防治疗率低[J].中华医学杂志,2009,89(2):137.
[5]Yuanhua Yang,Lirong Liang,Zhenguo Zhai,et al.Pulmonary Embolism Incidence and Fatality Trends in Chinese Hospitals from 1997 to 2008:A Multicenter Registration Study[J].PLo S ONE,2011,6(11):134-137.
[6]ChauKY,YuenST,WongMP(1997)ClinicopathologicalpatternofpulmonarythromboembolisminChineseautopsypatients:comparisonwithCaucasianseries[J].Pathology29:263-266.