[抗磷脂综合征患者纤溶酶原激活物抑制剂1基因多态性与血栓形成]

[Plasminogen activator inhibitor type 1 gene polymorphism and thromboses in patients with antiphospholipid syndrome].

作者信息

Reshetniak T M, Ostriakova E V, Patrusheva N L, Patrushev L I, Aleksandrova E N, Seredavkina N V, Volkov A V, Nasonov E L

出版信息

Ter Arkh. 2013;85(1):76-84.

PMID:23536951

Abstract

AIM

To estimate the prevalence of plasminogen activator inhibitor type 1 (PAI-1) gene polymorphism in patients with antiphospholipid syndrome (APS) and its implication in vascular disorders.

SUBJECTS AND METHODS

The investigation enrolled 138 patients: 103 with APS, including 47 with systemic lupus erythematosus (SLE) + APS and 56 with primary APS (PAPS), 15 with SLE without APS, 20 with idiopathic thrombosis (IT), a control group (30 apparently healthy individuals). Thrombosis at various sites was recorded in 91 (88%) of the 103 patients with APS. The authors analyzed both the presence of thrombotic events in all the groups and the number of cases of thrombosis in each patient. Antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin antibodies, and anti-beta2-glycoprotein type 1 antibodies, were studied in all the patients. To diagnose a genotype in patients by the code encoding for PAI-1, DNA isolated from peripheral blood by standard methods was used and further investigated by real-time polymerase chain reaction.

RESULTS

Out of 91 patients with APS and thrombosis, 27 (30%) had the 4G/4G genotype, which corresponded to homozygous mutation in the PAI-1 gene, 50 (55%) had the 4G/5G genotype (heterozygous mutation), and 14 (15%) had the 5G/5G (a normal genotype). The PAI-1 4G/5G genotype was present in 22 (70%) of 31 patients with SLE + APS and lower limb deep vein thrombosis versus 17 (470%) of 36 patients with PAPS (odds ratio (OR) 2.73; 95% confidence interval (CI), 0.89 to 8.59; p = 0.08) and in 9 (90%) of 10 patients with SLE + APS and pulmonary artery thromboembolism versus 8 (40%) of 20 patients with PAPS (OR 13,5; 95% CI, 1.23 to 344.98; p = 0.02). The incidence of thrombosis per 100 person-years was higher in the PAI-1 4G/4G and 4G/5G groups: 35.4 and 28.1 cases per 100 person-years, respectively. Thromboses were least often in the group of patients with the PAI-1 5G/5G genotype (18.6).

CONCLUSION

The prevalence of the PAI-1 5G/5G genotype in patients with APS and thrombosis was significantly lower than in those with SLE without APS or thrombosis. The 4G/5G polymorphism in APS in the presence of SLE was associated with venous thromboembolisms whereas in PAPS there was no relationship between the PAI-1 genotype, a history of thrombosis, and its localization.

摘要

目的

评估抗磷脂综合征（APS）患者中纤溶酶原激活物抑制剂1型（PAI - 1）基因多态性的患病率及其在血管疾病中的意义。

对象与方法

该研究纳入了138例患者：103例APS患者，其中包括47例系统性红斑狼疮（SLE）合并APS患者和56例原发性APS（PAPS）患者，15例无APS的SLE患者，20例特发性血栓形成（IT）患者，以及一个对照组（30名明显健康的个体）。103例APS患者中有91例（88%）记录了不同部位的血栓形成。作者分析了所有组中血栓事件的存在情况以及每位患者的血栓形成病例数。对所有患者研究了抗磷脂抗体，如狼疮抗凝物、抗心磷脂抗体和抗β2糖蛋白1型抗体。为通过PAI - 1编码诊断患者的基因型，使用标准方法从外周血中分离DNA，并通过实时聚合酶链反应进一步研究。

结果

在91例有血栓形成的APS患者中，27例（30%）具有4G/4G基因型，对应PAI - 1基因的纯合突变，50例（55%）具有4G/5G基因型（杂合突变），14例（15%）具有5G/5G（正常基因型）。31例SLE合并APS且有下肢深静脉血栓形成的患者中，22例（70%）存在PAI - 1 4G/5G基因型，而36例PAPS患者中有17例（47%）存在该基因型（优势比（OR）2.73；95%置信区间（CI），0.89至8.59；p = 0.08）；10例SLE合并APS且有肺动脉血栓栓塞的患者中有例9（90%）存在该基因型，而20例PAPS患者中有8例（40%）存在该基因型（OR 13.5；95% CI，1.23至344.98；p = 0.02）。PAI - 1 4G/4G和4G/5G组每100人年的血栓形成发生率更高：分别为每100人年35.4例和28.1例。血栓形成最少见于PAI - 1 5G/5G基因型的患者组（18.6例）。