纤溶酶原激活剂抑制物-1基因启动子区4G/5G多态性与血栓性疾病的

The correlation between 4G/5G polymorphism located in the promoter region of PAI-1 gene and thrombotic disease

目的 研究纤溶酶原激活剂抑制物 1(plasminogenactivatorinhibitor 1,PAI 1)基因启动子区单核苷酸插入 /缺失 (4G/ 5G)多态性和血浆PAI 1活性与血栓性疾病之间的关系。方法 病例组 :2 35例有心绞痛史的患者 ,2 0 0例心肌梗死患者 ,71例脑梗塞患者。对照组 :30 2例正常人。分别进行PAI 1基因启动子区 4G/ 5G多态性分析 ,并对其中 116例患者和 90例正常人进行血浆PAI 1活性测定 ,同时检测血糖、血脂、血压、体重指数。用酚、氯仿方法抽提DNA。血浆PAI 1活性测定采用发色底物法。结果 (1)病例组与对照组比较 ,4G/ 4G基因型频率较高 ,差异有显著性 (P =0 .0 2 2 ) ;(2 ) 4G/5G基因多态性与血浆PAI 1活性存在显著相关性 (P =0 .0 0 1) ,以 4G/ 4G基因型血浆PAI 1活性最高 ;(3)病例组 4G/ 4G基因型的血浆PAI 1活性与血糖、甘油三酯存在相关性 ;(4 ) 4G/ 4G基因型的血浆PAI 1同时与血糖、甘油三酯、胆固醇、体重指数成正相关。结论 病例组 4G/ 4G基因型频率较高 ,血浆PAI 1活性较高 ,其血浆PAI 1活性与血糖、甘油三酯、胆固醇、体重指数存在基因依赖关系 。

Objective To study the correlation between a single nucleotide insertion/deletion (4G/5G) polymorphism located in the promoter region of PAI 1 (plasminogen activator inhibitor 1) gene, plasma PAI 1 activity and thrombotic disease. Methods 4G/5G polymorphism were simultaneously measured in 235 patients with angina pectoris (AP), 200 patients with myocardial infarction (MI), 71 patients with cerebral infarction and 302 people as control subjects. The plasma PAI 1 activity was studied in 116 patients and 90 control subjects. In the meantime blood glucose, blood lipids, blood pressure, body mass index (BMI) were studied. DNA was extracted with the phenol/chloform method. The plasma PAI 1 activity was assayed with chromogenic substrate. Results (1) The frequencies of the genotype 4G/4G were higher in patients with AP, MI and cerebral infarction than that in control subjects ( P =0.022). (2) 4G/5G polymorphism were significantly associated with plasma PAI 1 activity( P =0.00?1). The genotype(4G/4G) showed that plasma PAI 1 activity was the highest in patients with AP, MI and cerebral infarction. (3) Plasma PAI 1 activity in patients group of the genotype (4G/4G) was associated with blood glucose, triglyceride.(4) Plasma PAI 1 activity of the genotype (4G/4G) was positively associated with blood glucose, triglyceride, cholesterol, and BMI at the same time. Conclusion The frequencies of the genotype 4G/4G were higher in patients as compared with control subjects. Plasma PAI 1 activity of the genotype(4G/4G) was significantly increased and associated with blood glucose, triglyceride, cholesterol and BMI. It may be one of the major factors in patients with thrombotic disease.