Wang Ziran, Kong Lingjun, Luo Guoju, Zhang Han, Sun Fengchun, Liang Wenjuan, Wu Wei, Guo Zijian, Zhang Rui, Dou Yaling
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Clinical Laboratory, Affiliated Hospital of Jining Medical University, Shandong Province, Jining, China.
Thromb J. 2022 Nov 14;20(1):68. doi: 10.1186/s12959-022-00430-x.
Venous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE.
A total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously.
The TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group.
The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.
静脉血栓栓塞症（VTE）是一种危及生命的心血管综合征，其特征是止血与血栓形成失衡以及血管内血栓形成。本研究的目的是阐明PAI-1 4G/5G多态性对中国VTE患者的临床影响。
在北京协和医院招募了169名受试者（89名VTE患者、10名高胆红素血症患者、10名高脂血症患者和60名健康对照）。以测序法作为金标准，评估TaqMan-MGB RT-PCR法检测F5 G1691A（FVL）和PAI-1 4G/5G多态性的准确性。此外，探讨PAI-1 4G/5G多态性与中国人群VTE易感性、治疗效果及复发状态的相关性。最终，同时对另外64名受试者（32名VTE患者和32名健康对照）测定血浆PAI-1抗原水平和PAI-1 4G/5G多态性。
TaqMan-MGB RT-PCR法被证明在确定FVL和PAI-1 4G/5G多态性方面具有高度准确性，不受样品中胆红素和脂质的干扰。在本研究中，使用五种遗传模型（等位基因、基因型、显性、隐性和加性）均未观察到PAI-1 4G/5G多态性与VTE之间存在明显相关性。此外，我们还观察到4G/5G基因型个体的中性粒细胞计数和中性粒细胞与淋巴细胞比值（NLR）低于5G/5G基因型个体。此外，我们发现5G/5G基因型患者比4G/4G基因型患者更有可能实现完全再通。此外，与4G/4G或4G/5G基因型个体相比，携带5G/5G基因型的个体更有可能处于无复发状态。VTE组的PAI-1抗原水平显著高于健康对照组。然而，VTE组或健康对照组中携带不同基因型的受试者之间PAI-1抗原水平无显著差异。
PAI-1 4G/5G多态性在评估中国VTE患者的预后方面具有潜在价值。我们的研究为PAI-1 4G/5G多态性在VTE患者的个体化管理和监测中的应用奠定了基础。
