纤溶酶原激活物抑制剂-1启动子区域基因多态性与肺血栓栓塞症的相关性研究

Relationship between polymorphisms of plasminogen activator inhibitor-1 promoter gene and pulmonary thromboembolism in Chinese Han population

目的探讨纤溶酶原激活物抑制剂-1(PAI-1)基因启动子区域-675位点单核苷酸缺失/插入(4G/5G)多态性与PTE发生的相关性。方法采用病例-对照研究,病例组为经放射性核素肺通气/灌注显像、螺旋CT肺动脉造影(CTPA)检查并结合临床资料确诊的PTE患者101例;对照组为来自PTE患者相同地区汉族人群,101例,性别、年龄相匹配。应用碘化钾-氯仿-异丙醇法提取基因组。联合应用聚合酶链反应(PCR)、变性高效液相色谱分析(DHPLC)和DNA直接测序分析PAI-1基因启动子区域的4G/5G多态性。结果PAI-1基因4G和5G等位基因频率在对照组分别为0·495和0·505,基因型分布符合Hardy-Weinberg平衡定律。4G4G、4G5G、5G5G基因型在PTE病例组分别为58(57·4%)、32(31·7%)、11(10·9%);对照组分别为31(30·7%)、38(37·6%)、32(31·7%),χ2=18·961,差别有统计学意义。病例组与对照组4G等位基因频率分别为0·733、0·495,5G等位基因分别为0·267,0·505,χ2=24·060,差别有统计学意义。单变量Logistic回归探讨PAI-1基因4G/5G与PTE的关系,4G4G+4G5G、4G4G、4G5G的OR值分别为3·794(1·786-8·060)、5·443(2·416-12·260)、2·450(1·067-5·623);P值分别为0·001、0·000、0·035。结论PAI-1启动子区域4G/5G、4G/4G基因型与PTE的发生有关,4G/5G、4G/4G基因型个体表现为更高的PTE危险性。

Objective To determine the prevalence of polymorphisms in the plasminogen activator inhibitor-1 （ PAI-1） promoter 4G/SG polymorphisms in Chinese Han population and to investigate whether they are associated with pulmonary thromboembolism （ PTE ）. Methods Samples of peripheral venous blood were collected from 101 patients with FIE diagnosed by high probability of lung ventilation/perfusion scan and/or multi-slice CT pulmonary angiography （CTPA） as well as medical history and clinical manifestations, 67 males and 34 females, aged 48±15, and 101 age and sex-matched healthy controls from the same geographic area as controls. The genome DNA was extracted from the whole blood using potassium iodide--phenol-chloroform method. Polymerase chain reaction （PCR） , denaturing high performance liquid chromatography（DHPLC） , and sequence analysis were used to screen the single nucleotide polymorphisms and the genotype distribution of -675 4G/5G located in the promoter region of the PAI-1 gene. Results The frequencies of the allele 4G of PAI-1 gene in the controls were 0. 495, significantly lower than in the PIE patients （0.733, χ^2 =24.060, P〈0.01 ）. The frequencies of the allele 5G of PAI-1 gene in the controls were 0.505, significantly higher than that in the PET patients. The genotype frequency of 4G4G of the PET patients was 57.4%, significantly higher than that of the controls （30.7% , P=0.000）. The genotype frequencies of 4GSG and 5GSG of the PET patients were 31.7% and 10.9% respectively, not significantly different from those of the controls （37.6 and 31.7% respectively）. The presence of 4G allele of PAI-1 gene was found to be a greater risk factor for PTE. In comparison with the controls, the OR of 4G4G ＋4G5G, 4G4G, and 4G5G in the PET patients were 3. 794 （ 1. 786-8. 060）, 5. 443 （2.416-12. 260）, and 2.450 （ 1. 067-5. 623 ） respectively with the P values of 0. 001, 0. 000, and 0. 035 respectively. Conclusion The 4G/5G and 4G/4G genotypes are associated with the pathogenesis of PET. T.