Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphisms and risk of venous thromboembolism – a meta-analysis and systematic review

Abstract

Summary: Background: A 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene has been reported to enhance the plasma levels of PAI-1, which plays an important role in fibrinolysis disorders and venous thromboembolism, but a large number of studies have reported inconclusive results. Therefore, we performed a meta-analysis to analysis these associations. Materials and methods: We performed a publication search for articles published before April 2019 by using the electronic databases of web of Science, Embase, PubMed, CNKI, CBM and WanFang data with the following terms “PAI-1”, “polymorphism”, “Venous Thromboembolism”. Two investigators independently extracted data and assessed study quality. Statistical analyses were undertaken using Stata 14.0. Results: A total of 27 studies, with 3135 patients and 5346 controls were included. Overall, the variant PAI-1 4G/4G and PAI-1 4G/5G was associated with venous thromboembolism risk, compared with the PAI-1 5G/5G allele in the populations included in the analysis. Stratified analysis revealed that PAI-1 4G/4G and PAI-1 4G/5G genotypes were associated with an increased VTE risk among Asia populations in all five genetic models. Conclusions: The PAI-1 4G/5G polymorphism may be a potential biomarker of VTE risk, particularly in Asia populations. Further larger studies with multi-ethnic populations are required to further assess the association between PAI-1 4G/4G polymorphisms and VTE risk.

Relationship between ABO blood group and risk of venous thrombosis in cancer patients with peripherally inserted central catheters

“…[ 22 ] According to the evaluation content of Newcastle-Ottawa scale scale, they were divided into 8 items and 9 points, and each score was 1 point. [ 23 ]…”

Plasminogen activator inhibitor‐1: a potential etiological role in livedoid vasculopathy

“…The PAI-1 levels in the 4G/4G genotype were estimated to be approximately 25% higher than those in the 5G/5G genotype. 18 PAI-1 gene 4G/5G polymorphism is associated with many diseases, including venous thromboembolism, 5,19 polycystic ovary syndrome, 14 asthma, 20 myocardial infarction, 21 and LV. Some LV patients were successfully treated with tPA therapy, and sequencing results revealed that their PAI-1 genotypes were homozygous (4G/4G).…”

“…PAI-1 4G/5G gene polymorphism and elevated plasma levels of PAI-1 have been detected in venous thromboembolism, and PAI-1 may be a suitable biomarker for assessing the risk of venous thromboembolism. 5 In recent years, Agirbasli et al observed that increased mRNA expression of PAI-1 in cutaneous lesions of LV was highly associated with histological findings of ulcers. 6 Moreover, LV patients with PAI-1 promoter homozygosity (4G/4G) responded well to tissue plasminogen activator infusion therapy.…”

“…Plasminogen activator inhibitor (PAI)‐1 is an inhibitor of the endogenous fibrinolytic system in blood coagulation and has gradually drawn attention because of its potential role in the pathogenesis and mechanism of LV. PAI‐1 4G/5G gene polymorphism and elevated plasma levels of PAI‐1 have been detected in venous thromboembolism, and PAI‐1 may be a suitable biomarker for assessing the risk of venous thromboembolism 5 . In recent years, Agirbasli et al observed that increased mRNA expression of PAI‐1 in cutaneous lesions of LV was highly associated with histological findings of ulcers 6 .…”

Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms

“…22 The genotypes of this gene polymorphism are 4G4G, 4G5G, and 5G5G respectively, which regulate the expression level of PAI-1. 23,24 Abundant existing studies have confirmed that genotype 4G4G is related to the increase in PAI-I gene transcription. [25][26][27] As such, it is reason able to suppose that the plasma PAI-1 level is the highest in genotype 4G4G, which is followed by genotype 4G5G, and is the lowest in genotype 5G5G.…”