Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis

“…Here, we found no association between the genetically determined PAI-1 concentration and the risk of VTE, DVT, and PE. Zhang et al (2020) and Wang et al (2022) revealed the PAI-1 4G/5G polymorphism associated with the risk of the onset of VTE in East Asian ancestry, but the causal relationship between serum PAI-1 levels and VTE risk was not recognized in our study, probably because the GWAS data we assessed were generated from European ancestry. Because of variances in gene linkage disequilibrium among races, SNPs indicating PAI-1 levels in GWAS studies of European populations do not reflect PAI-1 levels in other races.…”

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough

“…Many research are looking into the relationship between PAI-1 4G/5G polymorphisms and a variety of disorders, such as thrombosis (Zhang et al, 2020a), systemic lupus erythematosus (Anaya-Macias et al, 2020), thyroid eye disease (Katko et al, 2021), metabolic syndrome (Zhang et al, 2020b) and many more. Previous research from our center has shown that the PAI-1 4G/ 5G polymorphism may be useful for determining the prognosis of Chinese patients with venous thromboembolism (Wang et al, 2022).…”

“…Nevertheless, the field of allergic diseases had few Frontiers in Genetics frontiersin.org corresponding reports. TaqMan-MGB qPCR offered a reliable and affordable method for investigating SNPs with allergy disorders (Wang et al, 2021;Jin et al, 2022;Wang et al, 2022). Using this technology, we initially discovered that patients with allergic cough had a different distribution of the PAI-1 rs1799762 gene than healthy people.…”

“…According to the Applied Biosystems methodology, genotyping was accomplished by TaqMan chemistry utilizing the real-time Prism 3730XL Sequence Detection System (ABI Inc. CA, United States). In our prior research, we have demonstrated the effectiveness of the TaqMan-MGB qPCR kit for the detection of gene polymorphisms (Wang et al, 2021;Jin et al, 2022;Wang et al, 2022). The Kappa test was used to examine the agreement between DNA sequencing and TaqMan-MGB qPCR, with a Kappa value of 1 and a p-value <.001.…”

What is the impact of plasminogen activator inhibitor type 1 (PAI-1) gene polymorphism on gynecological malignancies: a retrospective study

“…At present, the application prospects of PAI-1 in clinical practice are very broad, not only in gynecological malignant tumors, but be of great signi cance for the screening, diagnosis, evaluation of treatment responses, and prediction of prognosis for various diseases. PAI-1 is an important factor in regulating the formation of thrombi in the blood vessels, and it plays an important role in the prevention and treatment of cardiovascular diseases.By inhibiting the PAI-1, it can effectively prevent and treat the occurrence of some diseases, such as cardiovascular diseases and stroke [17] .A great deal of studies have also shown that serum PAI-1 level is closely related to the growth, metastasis, and invasion of tumors. At the same time, PAI-1 level can be used to screen early stage of lung cancer and predict treatment response of breast cancer [18] .…”