PAI-1启动子区4G/5G基因多态性与脑血管病相关性研究

The study of PAI-1 promotor region gene polymorphism in cerebrovascular disease

目的 :初步探讨人类纤溶酶原激活物抑制物 1(plasminogenactivatorinhibitor,PAI 1)启动子区基因多态性与脑血管病的关系及其在脑血管病发病过程中的作用。方法 :通过多聚酶链反应 (polymerasechainreaction ,PCR)技术和发色底物法(ELISA) ,测定 96例脑血管病病人 ,其中脑梗死 (cerebralinfarction ,CI)组 6 5例 ,脑出血 (cerebralhemorrhage ,CH)组 31例和 6 0例对照组的白细胞PAI 1启动子区 4G/ 5G多态性位点的基因型及血浆PAI 1活性。结果 :CI组血浆PAI 1活性明显高于其它二组 ,各组中均以纯合子 4G/ 4G基因型患者的PAI 1血浆活性水平为最高 ,5G/ 5G基因型最低 ,杂合子 4G/ 5G基因型居中 ;4G纯合子基因型与其它二型之间比较差异均有显著意义 ,4G/ 5G与 5G/ 5G基因型之间比较差异无显著意义。CI组 4G/ 4G纯合子型基因型与对照组 (Controls)比较有显著性差异 (P <0 0 5 ) ,CI组基因型与CH组及CH组与对照组基因型比较均无统计学意义 (P >0 0 5 )。女性CI 4G纯合子基因型患者血浆PAI 1活性与同型男性患者比较有显著性差异。结论 :纯合子 4G/ 4G基因型可能是CI发病的危险因素之一 ,4G纯合子个体可能具有较高的CI发病倾向 。

Objective:To investigate the relationship between the plasminogen activator inhibitor 1(PAI 1) gene polymorphism and cerebrovascular disease and whether it played an important role in the pathogenesis of cerebrovascular disease Methods:The 4G/5G allele polymorphism in the PAI 1 gene promotor region were genotyped by polymerase chain reaction (PCR) from peripheral blood leukocytes from 60 normal controls, 65 patients with acute cerebral infarction and 31 hypertensives complicated with cerebral hemorrhage Their plasma PAI 1 activity were assayed by ELISA Results: The plasma PAI 1 activity level in the CI group was significantly higher than those in the other two groups PAI 1 level was significantly higher in 4G allele homozygous than both those in 4G/5G heterozygous and 5G homozygous Although PAI 1 level was higher in 4G/5G heterozygous than that in 5G homozygous, the difference had not reach statistically significant There were significant differences between acute cerebral infarction PAI 1 gene polymorphism and controls (P<0 05), and the frequencies of 4G/4G genotype among patients with acute cerebral infarction (43 08%) were higher than those of normal controls (20 00%, P<0 05) There were no significant differences between hypertensives complicated with hemorrhage (25 81%) and controls (P>0 05), and PAI 1 levels of the 4G/4G genotype among female patients with CI were higher than those of the male patients with CI of the same genotype Conclusion: The results suggest that PAI 1 gene polymorphism may be a susceptible factor to acute cerebral infarction in Chinese, and 4G allele homozygous genotype may be the major risk factor of acute cerebral infarction, especially it may be an independent risk factor of female CI patients