Investigation of Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G promoter polymorphism and other thrombophilia genes in patients with acute pulmonary embolism
Authors: Civirjic C I , Diaconu N , Grosu A , Sorici G , Cuzor T 
Published: November 2023

Abstract

Background
Venous thromboembolism (VTE) is a serious threat to life and health, commonly known as the silent killer. Recent study has found that VTE is a polygenetic disease and more than 60% of deep vein thrombosis risk is influenced by genetic factors [1]. PAI-1 is a serine protease with negative feedback to fibrinolysis, activating and inhibiting coagulation [2]. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism and other thrombophilia in patients with acute PE.

Methods
A total of 58 subjects with acute PE and 60 healthy controls, were recruited in Institute of Cardiology. The accuracy of the RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Moreover, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status were explored. Eventually, we evaluated the association with inherited thrombophilia genes, such as the coagulation Factor V Leiden, prothrombin G20210A, FGB-455 G/A and methylenetetrahydrofolate reductase C677T and 1298 A/C.

Results
It was noted that the vast majority of patients with acute PE (87.9%) present polymorphism in the PAI-1 gene (29.3% homozygous (4G/4G) and 58.6% heterozygous (5G/4G)). Eleven patients out of 58 (19% of patients) showed factor V Leiden mutation and 19 patients out of 58 (32,7% of patients) showed mutation in FGB-455 G/A (2 homozygotes); MTHFR C677T gene mutation was found in 55,2%, while prothrombin 20210A gene mutation was presented in 6 patients (10.3% of patients). Nine patients (15,5% of patients) presented with chronic complication of VTE and 38.7% of patients showed recurrent pulmonary embolism. More than a half of patients (51.9%) had multiple gene mutation and only one presented with mutations in three studied genes. It showed a significant difference in the occurrence of other thromboses in the body and significant increase in the recurrence of pulmonary embolism and residual complications in these patients. It was 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, it was underlined that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. Individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to those 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.

Conclusion
The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of patients with VTE. This study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE. According to this study results PAI-1 4G/5G polymorphism could be included in laboratory testing panel of thrombophilia.