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

Ziran Wang; Lingjun Kong; Guoju Luo; Han Zhang; Fengchun Sun; Wenjuan Liang; Wei Wu; Zijian Guo; Rui Zhang; Yaling Dou

doi:10.1186/s12959-022-00430-x

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

Thromb J. 2022 Nov 14;20(1):68. doi: 10.1186/s12959-022-00430-x.

Authors

Ziran Wang^#¹, Lingjun Kong^#¹, Guoju Luo¹, Han Zhang¹, Fengchun Sun², Wenjuan Liang³, Wei Wu¹, Zijian Guo¹, Rui Zhang¹, Yaling Dou⁴

Affiliations

¹ Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
² Department of Clinical Laboratory, Affiliated Hospital of Jining Medical University, Shandong Province, Jining, China.
³ Medical Laboratory Center, Northwest Women's and Children's Hospital, Shaxi Province, Xi'an, China.
⁴ Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. douyl@pumch.cn.

^# Contributed equally.

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.

Keywords: Gene polymorphism; PAI-1; Venous thromboembolism.

Abstract

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