[纤溶酶原激活物抑制剂-1启动子基因多态性与中国汉族人群肺血栓栓塞症的关系]

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

作者信息

Zhai Zhen-guo, Wang Chen, Yang Yuan-hua, Pang Bao-sen, Xiao Bai, Liu Yan-mei, Mao Yan-ling, Weng Xin-zhi

机构信息

Beijing Institute of Respiratory Medicine, Beijing Chaoyang hospital, Capital University of Medical Sciences, 100020, Beijing, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2006 May 23;86(19):1313-7.

PMID:16796899

Abstract

OBJECTIVE

To determine the prevalence of polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G 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 PTE 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 PTE patients (0.733, chi(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 4G5G and 5G5G 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.

摘要

目的

确定中国汉族人群纤溶酶原激活物抑制剂-1（PAI-1）启动子4G/5G多态性的发生率，并研究其是否与肺血栓栓塞症（PTE）相关。

方法

收集101例经肺通气/灌注扫描高概率诊断和/或多层螺旋CT肺动脉造影（CTPA）以及病史和临床表现确诊的PTE患者的外周静脉血样本，其中男性67例，女性34例，年龄48±15岁，并选取来自同一地理区域的101例年龄和性别匹配的健康对照作为对照组。采用碘化钾-苯酚-氯仿法从全血中提取基因组DNA。运用聚合酶链反应（PCR）、变性高效液相色谱（DHPLC）和序列分析来筛选PAI-1基因启动子区-675 4G/5G的单核苷酸多态性及基因型分布。

结果

对照组中PAI-1基因4G等位基因频率为0.495，显著低于PTE患者（0.733，χ² = 24.060，P < 0.01）。对照组中PAI-1基因5G等位基因频率为0.505，显著高于PTE患者。PTE患者4G4G基因型频率为57.4%，显著高于对照组（30.7%，P = 0.000）。PTE患者4G5G和5G5G基因型频率分别为31.7%和10.9%，与对照组（分别为37.6%和31.7%）无显著差异。发现PAI-1基因4G等位基因是PTE的更大危险因素。与对照组相比，PTE患者中4G4G + 4G5G、4G4G和4G5G的比值比（OR）分别为3.794（1.786 - 8.060）、5.443（2.416 - 12.260）和2.450（1.067 - 5.623），P值分别为0.001、0.000和0.035。