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[抗磷脂综合征患者纤溶酶原激活物抑制剂1型基因多态性、纤溶酶原水平与血栓形成]

[Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen level and thrombosis in patients with antiphospholipid syndrome].

作者信息

Aĭsina R B, Mukhametova L I, Ostriakova E V, Seredavkina N V, Patrushev L I, Patrusheva N L, Reshetniak T M, Gulin D A, Gershkovich K B, Nasonov E L, Varfolomeev S D

出版信息

Biomed Khim. 2014 Jan-Feb;60(1):72-93. doi: 10.18097/pbmc20146001072.

Abstract

The frequency of venous and arterial thromboses and plasminogen level were investigated in 78 patients with antiphospholipid syndrome (APS), 35 of whom with systemic lupus erythematosus (SLE+APS) and 43 - with primary APS (PAPS). The levels and genotype of plasminogen activator inhibitor type 1 (PAI-1) were determined in 45 patients with APS, of whom 21 patients with SLE + APS and 24 patients with PAPS. A control group included 10 healthy individuals without autoimmune disease signs and thromboses on period of investigation and in past history. It was shown for the first time that for one third of 67 patients with APS and thromboses high positive levels of antiphospholipid antibodies (aPL) are associated with low plasminogen levels. The levels of PAI-1 antigen measured by ELIZA method, which detects active, latent and bound with plasminogen activator PAI-1, were opposed with frequency of thromboses in APS patients. Correlation between the high and increased levels of PAI-1 and high positive aPL levels was found for one third of 43 patients with APS and thrombosis. One of the possible mechanisms of this interconnection was considered. It was shown that arterial and, to a more extent, venous thromboses are associated with the 4G/5G polymorphism of PAI-1 gene and high plasma level of the inhibitor in 79% of APS patients. At the presence of the 4G allele patients with SLE+APS had higher PAI-1 levels than patients with PAPS. The obtained results show that measuring the levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of PAI-1 gene which is associated with thromboses may have the practical significance for identification of high risk of thrombosis in APS patients.

摘要

对78例抗磷脂综合征(APS)患者的静脉和动脉血栓形成频率及纤溶酶原水平进行了研究,其中35例合并系统性红斑狼疮(SLE+APS),43例为原发性APS(PAPS)。对45例APS患者测定了纤溶酶原激活物抑制剂1型(PAI-1)的水平及基因型,其中21例为SLE+APS患者,24例为PAPS患者。对照组包括10名在研究期间及既往无自身免疫性疾病体征和血栓形成的健康个体。首次发现,在67例有血栓形成的APS患者中,三分之一抗磷脂抗体(aPL)高阳性水平与低纤溶酶原水平相关。用ELISA法检测活性、潜伏性及与纤溶酶原激活物结合的PAI-1所测得的PAI-1抗原水平,与APS患者的血栓形成频率呈相反关系。在43例有血栓形成的APS患者中,三分之一发现PAI-1高水平及升高水平与aPL高阳性水平之间存在相关性。探讨了这种相互联系的一种可能机制。结果显示,在79%的APS患者中,动脉血栓形成,在更大程度上静脉血栓形成与PAI-1基因的4G/5G多态性及该抑制剂的高血浆水平相关。存在4G等位基因时,SLE+APS患者比PAPS患者的PAI-1水平更高。所得结果表明,测定纤溶酶原和PAI-1水平以及与血栓形成相关的PAI-1基因的4G/5G多态性,对于识别APS患者的高血栓形成风险可能具有实际意义。

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