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

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。

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/SG 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/SG 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 statistical difference 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 middie, 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 environmerit. However, the environment may have an effect on the PAI-1 expression, but PAI-1 polymorphism is more important than the environment.