scholarly journals Specific Polymorphism 4G/5G Gene for PAI-1 as a Possible Cause of Cerebral Venous Thrombosis: A Case Report

2017 ◽  
Vol 18 (2) ◽  
pp. 169-173
Author(s):  
Tatjana Boskovic Matic ◽  
Aleksandar Gavrilovic ◽  
Snezana Simovic ◽  
Dejan Aleksic ◽  
Katarina Vesic ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Cerebral Venous Thrombosis ◽  
Sinus Thrombosis ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Sagittal Sinus ◽  
Clinical Center ◽  
The Impact ◽  
Activator Inhibitor

AbstractThrombosis of veins and venous sinus (CVT) is the rare cerebral vascular disorder which makes less than 1% of all strokes. Thrombosis of veins and venous sinuses is picturesquely called “мајоr neurological forger” since it is characterized by very varied clinical picture. Among the various causes of CVT, which can be of infective or non-infective nature, the congenital hyper coagulations especially stand out, diagnosis is based on highly sophisticated diagnostic tests.We present the case of a female patient, 36 years old, who was hospitalized at the Clinic for Neurology in Clinical Center because of the diffuse headache she had for the last few days, with milder right-sided hemiparesis and one generalized tonic-clonic epileptic seizure. With nuclear magnetic resonance (MR/2D venography) the thrombosis of the upper and lower sagittal sinuses is confirmed. By appropriate laboratory tests, as well as by confirmatory immunological and genetic analyses, the impact of the most of the factors is excluded which can contribute to the occurrence of venous thrombosis. The only pathological findings which indicated the possible congenital thrombophilia as the cause of the sagittal sinus thrombosis was the determination of the specific polymorphism of the 4G/5G gene for plasminogen activator inhibitor 1.According to our knowledge, this is the first decribed case of the possible impact of the specific polymorphism of the 4G/5G gene for plasminogen activator inhibitor of 1 on the development of cerebral venous thrombosis.

scholarly journals The Impact of the Gene Variants FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G on Pregnancy Loss in Women from Central Serbia

2020 ◽  
Vol 21 (1) ◽  
pp. 19-25
Author(s):  
Gordana M. Sosic ◽  
Snezana Sretenovic ◽  
Danijela Radivojevic ◽  
Nikola Jovic ◽  
Mirjana Varjacic
Keyword(s):  
Plasminogen Activator ◽  
Pregnancy Loss ◽  
Methylenetetrahydrofolate Reductase ◽  
Plasminogen Activator Inhibitor ◽  
Gene Variants ◽  
Plasminogen Activator Inhibitor 1 ◽  
Inherited Thrombophilia ◽  
Factor Ii ◽  
The Impact ◽  
Activator Inhibitor

AbstractThrombophilia is a condition of enhanced functionality of the haemostatic system with an increased tendency for thrombosis, and it can be a congenital, acquired, or complex defect. Pregnancy can be the cause of acquired transitory thrombophilia, which may lead to complications if inherited thrombophilia is also present.The aim of this study was to determine the genetic structure of the population based on the frequency of the gene variants factor V Leiden G1691A, factor II G20210A, methylenetetrahydrofolate reductase C677T, and plasminogen activator inhibitor-1 4G/5G, as well as to investigate the predictive value of these gene variants in repeated miscarriages.The study included 87 female patients from Central Serbia with an average age of 32.7±4.5 years with inherited thrombophilia and previous miscarriages, with or without intrauterine foetal death. The exclusion criteria included the existence of gynaecological and infectious aetiology and the deficit of factors important for the coagulation process.The resulting genotypes were in Hardy-Weinberg equilibrium. The frequency of genotypes with mutated alleles was significantly higher in this group of patients than in the control group for all variants except factor II G20210A. The most commonly mutated alleles were the plasminogen activator inhibitor-1 4G allele (0.61) and methylenetetrahydrofolate reductase T allele (0.47). Double mutation of plasminogen activator inhibitor-1 4G/5G and methylenetetrahydrofolate reductase C677T was dominant in patients with recurrent pregnancy loss (46.15%).The presence of a combination of genetic variants of the plasminogen activator inhibitor-1 4G/5G and methylenetetrahydrofolate reductase C677T is a significant predictor of spontaneous abortions in women with inherited thrombophilia in Central Serbia.

Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis

2007 ◽  
Vol 97 (06) ◽  
pp. 907-913 ◽  
Author(s):  
Argirios Tsantes ◽  
Pantelis Bagos ◽  
Evdoxia Rapti ◽  
Georgios Mantzios ◽  
Violeta Kapsimali ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Genetic Risk ◽  
Plasminogen Activator Inhibitor ◽  
Genetic Risk Factor ◽  
Published Data ◽  
Antiphospholipid Antibody ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

SummaryThe effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068–1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR:1.833,95% CI:1.325–2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.

The association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 gene and deep venous thrombosis in young people

2005 ◽  
Vol 20 (1) ◽  
pp. 48-52 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  
Keyword(s):  
Young People ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Activator Inhibitor ◽  
Pai 1

Objective: To evaluate the association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene and deep venous thrombosis (DVT) in young people. Methods: Prevalence of the 4G/5G polymorphism was investigated using DNA analysis in a population of 81 consecutive and unrelated patients with an objectively documented first episode of DVT under 40 years old and in a control group of 88 healthy subjects. Results: The frequency of genotypes among patients was 0.27 4G/4G, 0.49 4G/5G and 0.23 5G/5G, corresponding to a frequency of 0.52 for the 4G allele. In the control group the results were, respectively, 0.24, 0.44 and 0.32, corresponding to a frequency of 0.46 for the 4G allele. The odds ratio (OR) for homozygous 4G genotype was 1.5 (95% confidence interval: 0.7–3.6), which was not statistically significant ( P = 0.51). Conclusion: In this study, the 4G/5G polymorphism in the promoter of the PAI-1 gene, including the homozygous 4G genotype, was not associated with a significantly increased risk of DVT in young people.

OC-11 Plasminogen activator inhibitor 1 enhances venous thrombosis in pancreatic cancer

2021 ◽  
Vol 200 ◽  
pp. S10-S11
Author(s):  
Y. Hisada ◽  
K.B. Garratt ◽  
A. Maqsood ◽  
S.P. Grover ◽  
T. Kawano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

scholarly journals Plasminogen activator inhibitor 1 and venous thrombosis in pancreatic cancer

2021 ◽  
Vol 5 (2) ◽  
pp. 487-495
Author(s):  
Yohei Hisada ◽  
Kenison B. Garratt ◽  
Anaum Maqsood ◽  
Steven P. Grover ◽  
Tomohiro Kawano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Venous Thrombosis ◽  
Cancer Patients ◽  
Plasminogen Activator ◽  
Cell Lines ◽  
Plasminogen Activator Inhibitor ◽  
Pancreatic Tumors ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Pancreatic cancer patients have a high risk of venous thromboembolism (VTE). Plasminogen activator inhibitor 1 (PAI-1) inhibits plasminogen activators and increases the risk of thrombosis. PAI-1 is expressed by pancreatic tumors and human pancreatic cell lines. However, to date, there are no studies analyzing the association of active PAI-1 and VTE in pancreatic cancer patients. We investigated the association of active PAI-1 in plasma and VTE in pancreatic cancer patients. In addition, we determined if the presence of human pancreatic tumors expressing PAI-1 impairs venous thrombus resolution in mice. Plasma levels of active PAI-1 in patients with pancreatic cancer and mice bearing human tumors were determined by enzyme-linked immunosorbent assay. We measured PAI-1 expression in 5 different human pancreatic cancer cell lines and found that PANC-1 cells expressed the highest level. PANC-1 tumors were grown in nude mice. Venous thrombosis was induced by complete ligation of the inferior vena cava (IVC). Levels of active PAI-1 were independently associated with increased risk of VTE in patients with pancreatic cancer (subdistribution hazard ratio per doubling of levels: 1.39 [95% confidence interval, 1.09-1.78], P = .007). Mice bearing PANC-1 tumors had increased levels of both active human and active mouse PAI-1 and decreased levels of plasmin activity. Importantly, mice bearing PANC-1 tumors exhibited impaired venous thrombus resolution 8 days after IVC stasis compared with nontumor controls. Our results suggest that PAI-1 contributes to VTE in pancreatic cancer.

scholarly journals Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zachary M. Huttinger ◽  
Laura M. Haynes ◽  
Andrew Yee ◽  
Colin A. Kretz ◽  
Matthew L. Holding ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Genomic Sequence ◽  
Plasminogen Activator Inhibitor ◽  
Single Amino Acid ◽  
Plasminogen Activator Inhibitor 1 ◽  
Missense Variants ◽  
The Impact ◽  
Activator Inhibitor ◽  
Pai 1

AbstractThe serine protease inhibitor (SERPIN) plasminogen activator inhibitor-1 (PAI-1) is a key regulator of the fibrinolytic system, inhibiting the serine proteases tissue- and urokinase-type plasminogen activator (tPA and uPA, respectively). Missense variants render PAI-1 non-functional through misfolding, leading to its turnover as a protease substrate, or to a more rapid transition to the latent/inactive state. Deep mutational scanning was performed to evaluate the impact of amino acid sequence variation on PAI-1 inhibition of uPA using an M13 filamentous phage display system. Error prone PCR was used to construct a mutagenized PAI-1 library encompassing ~ 70% of potential single amino acid substitutions. The relative effects of 27% of all possible missense variants on PAI-1 inhibition of uPA were determined using high-throughput DNA sequencing. 826 missense variants demonstrated conserved inhibitory activity while 1137 resulted in loss of PAI-1 inhibitory function. The least evolutionarily conserved regions of PAI-1 were also identified as being the most tolerant of missense mutations. The results of this screen confirm previous low-throughput mutational studies, including those of the reactive center loop. These data provide a powerful resource for explaining structure–function relationships for PAI-1 and for the interpretation of human genomic sequence variants.

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