纤溶酶原激活物抑制物-1基因4G/5G多态性与肺动脉血栓栓塞的关系

目的 探讨纤溶酶原激活物抑制物-1(PAI-1)基因4G/5G多态性与肺动脉血栓栓塞(PTE)的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测76例PTE患者和74例年健康对照者PAI-1基因多态性分布特征.比较两组基因型、等位基因频率分布,分析其遗传模式并观察各基因型对不同临床亚组的影响.结果 4G/4G基因型频率病例组(50.0%)明显高于对照组(24.3%)(P<0.01),4G/4G、4G/5G及5G/5G 3种基因型频率PTE组与对照组比较差异有统计学意义;4G等位基因频率病例组(72.4%)高于对照组(55.4%),4G和5G等位基因频率PTE组与对照组比较差异有统计学意义.与5G/5G及4G/5G基因型相比,4G/4G基因型显著增加个体肺栓塞危险(OR=3.40,P<0.01).无明确环境诱因组4G/4G基因型频率显著高于对照组(P=0.04),而有环境诱因组与对照组比较4G/4G基因型频率差异无统计学意义.结论 PAI-1基因多态性与肺栓塞有关,4G等位基因是隐性作用方式,4G/4G基因型显著增加无环境诱因个体肺栓塞危险.

Relationship between 4G/5G polymorphism of promoter of plasminogen activator inhibitor-1 gene and pulmonary thromboembolism

Objective To investigate the relationship between 4G/5G polymorphism in the promotor of plasminogen activator inhibitor-1 (PAI-1) gene and pulmonary thromboembolism (PTE). And to detect whether it plays an important role in the pathogenesis of PTE. Methods The 76 patients with PTE, 74 gender and age matched healthy controls were recruited in this study. Genome DNA was extracted from whole blood using phenol-chloroform. Subjects were genotyped for the 4G/ 5G polymorphism of PAI-1 gene using polymerase chain reaction and restriction fragment length polymorphism analysis. Results Significant difference was found in the frequency of 4G/4G genotype between PTE group and control group (50.0% vs.24.3%,P<0.01). And there were no significant differences in 4G/5G and 5G/5G genotype between the two groups. The 4G allele frequency was higher in PTE group than in control group (72.4% vs. 55.4% , P<0.01) . The recessive allele model was informative and the odd ratio of 4G/4G genotype was much higher than of other two genotypes (OR=3.40, P<0.01). Further stratification showed 4G/4G genotype was associated with high risk of PTE for those individuals without traditional environment risk factors. Conclusions The 4G/5G polymorphism of PAI-1 gene is associated with PTE and 4G allele is recessive. 4G/4G genotype increases the risk of PTE for individuals who have no traditional risk factors of PTE.