PAI-1基因多态性与脑梗死及再梗死的关系

The association of PAI-1 gene polymorphism with cerebral infarction and recurrent cerebral infarction

目的 探讨纤溶酶原激活物抑制物 - 1(PAI- 1)基因多态性与脑梗死及再梗死的关系。方法 对5 0例初次脑梗死 (FCI)患者、45例再次脑梗死 (RCI)患者及 6 0名健康对照者以发色底物分解法测定血浆PAI- 1活性、扩增片段长度多态性分析 PAI- 1基因启动子区 4G/ 5 G和第四内含子区 (CA) n序列多态性。结果患者血浆 PAI- 1活性 ,无论 FCI(1.13± 1.1AU/ ml)和 RCI(1.13± 0 .15 0 AU/ ml)均显著高于对照者 (0 .7±0 .2 5 AU/ m l) (均 P<0 .0 1) ;4G等位基因频率在两脑梗死组均显著高于对照者 (均 P<0 .0 1) ,且 RCI高于FCI(P<0 .0 5 ) ,并与血浆 PAI- 1活性升高及高血脂有关 ;短片段 (CA) n重复倾向于与血浆 PAI- 1活性升高相关联 ,长片段者在脑梗死特别是 RCI者中较少 ;4G等位基因的脑梗死患者中短片段 (CA) n频率较高。结论 PAI- 1基因启动子区 4G等位基因及第四内含子区 (CA) n二核苷酸重复数少可致血浆 PAI- 1活性升高 ,从而参与脑梗死特别是

Objective To investigate the association of the gene polymorphism of plasminogen activator inhibitor 1 (PAI 1) with the cerebral infarction and recurrent cerebral infarction (RCI). Methods The plasma PAI 1 activity, by means of chromgenic substrate assay, and the sequence polymorphisms of 4G/5G in promotor region and (CA)n dinucleotide repeats in the 4th intron of PAI 1 gene, by amplified fragment length polymorphism assay, were measured in 50 patients with first ever cerebral infarction (FCI), 45 patients with RCI and 60 healthy controls.Results The plasma PAI 1 activities in both FCI patients (1.13±1 1 AU/ml) and RCI (1.13±0.150 AU/ml) were remarkably higher than that in the controls (0.7±0.25 AU/ml) (both P <0.01). The frequency of 4G allele in the patients was significantly higher than that in the controls, even higher in RCI than FCI. The 4G allele was associated with increased plasma PAI 1 activity and lipids, LDL, apoB. The shorter repeats of (CA)n was also related to higher PAI 1 activity. The longer repeats were more prevalent in the patients, especially in RCI patients. There was shorter repeats of (CA)n dinucleotide in the patients with 4G/4G genotype.Conclusion The 4G allele in the promotor region and shorter repeats of (CA)n in the 4th intron may result in the increased PAI 1 activity which may participate in the development of ischemic stroke, particularly FCI.