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冠心病患者纤维蛋白原Bβ448和纤溶酶原激活物抑制物-14G/5G基因多态性分析

Polymorphisms of Fg Bβ448 and PAI-1 4G/5G in patients with coronary heart diseases

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【作者】 高辉葛汝村周海萍张敏

【Author】 GAO Hui1,GE Ru-cun1,ZHOU Hai-ping1,ZHANG Min2(1.Shandong Engineering Technological Research Center for Prevention and Treatment of Thrombotic Diseases,Jinan 250031,Shandong,China;2.Department of Respiratory Diseases,Shandong Provincial Hospital,Jinan 250021,Shandong,China)

【机构】 山东省血栓病防治工程技术研究中心山东省立医院呼吸内科 山东济南250031山东济南250031山东济南250021

【摘要】 目的:探讨冠心病(CHD)患者纤维蛋白原(Fg)含量与Fg Bβ448位点基因多态性及mRNA表达的关系,以及纤溶酶原激活物抑制物-1活性(PAI-1:A)及含量(PAI-1:Ag)与PAI-1 4G/5G基因多态性及mRNA表达的关系。方法:实验对象分为CHD组与正常对照组,分别测定血浆Fg含量(Clauss法)、PAI-1:A(发色底物法)和PAI-1:Ag(ELISA法),采用PCR-RFLP技术分析FgBβ448位点和PAI-1 4G/5G基因多态性,用RT-PCR法检测其mRNA的表达。结果:CHD患者FgBβ448位点不同基因型对Fg mRNA表达有不同影响,其中L/L基因型表达最高,其次为A/L,A/A表达最低;Fg mRNA的表达量与血浆Fg水平呈正相关,CHD患者基因型频率与对照组比较差异无统计学意义(P>0.05)。CHD患者不同基因型对PAI-1 mRNA表达的影响各异,其中4G/4G基因型mRNA表达最高,其次为4G/5G,5G/5G表达最低;PAI-1 mRNA的表达量与血浆PAI-1:A及PAI-1:Ag水平呈正相关,CHD患者PAI-1 4G/5G基因型出现频率高于对照组(P<0.05)。结论:CHD患者存在凝血系统功能亢进和纤溶系统功能降低,CHD患者Fg升高不仅与基因型有关,同时也与环境因素的影响有关,PAI-1升高尽管存在环境因素对基因表达的影响,但基因型的影响更为重要。

【Abstract】 Objective: To study the correlation between the Fg Bβ448 polymorphisms and their mRNA expression and fibrinogen(Fg) level,and the correlation between plasminogen activator inhibitor-1(PAI-1) 4G/5G polymorphisms and their mRNA expression and PAI-1 activity(PAI-1:A),PAI-1 antigen(PAI-1:Ag) level in patients with coronary heart disease(CHD).Methods: The subjects were divided into two groups: the control group and the CHD group.Contents of Fg(Clauss),PAI-1:A(Chromogenic assay) and PAI-1:Ag(ELISA) in the plasma were determined.PCR-RFLP was used to determine the Fg Bβ448 and the PAI-1 4G/5G polymorphisms,and RT-PCR was used to determine the expression of their mRNA.Results: This polymorphism is related to elevated Fg mRNA expression.The mRNA expression degree was as following: L/L genotype,the highest;A/L,the middle;and A/A,the lowest.There was a positive correlation between mRNA expression and plasma Fg level.The frequency of A/A genotype of Fg Bβ448 had no statisticaldifference between the CHD group and the control group(P>0.05).Different genotypes offered different effects on PAI-1 mRNA expression.Expression of the 4G/4G genotype was in the highest,of the 4G/5G genotype was in the middle,and the 5G/5G genotype was the lowest.The frequency of the 4G/5G genotype of PAI-1 was significantly higher in the CHD group than that in the control group(P<0.05),contributing to over-expression of PAI-1 mRNA.There was a positive correlation between mRNA expression and plasma PAI-1:A and PAI-1:Ag level.Conclusions: Patients with CHD are hyper coagulation and fibrinolysis deficient,but elevated Fg may be related to the gene type and the environment.However,the environment may have an effect on the PAI-1 expression,but PAI-1 polymorphism is more important than the environment.

  • 【文献出处】 山东大学学报(医学版) ,Journal of Shandong University(Health Sciences) , 编辑部邮箱 ,2007年05期
  • 【分类号】R541.4
  • 【被引频次】3
  • 【下载频次】77
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