Detection of plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism in women with recurrent abortion

Background: recurrent abortion is considered one of the most common complications that occur during pregnancy and counts for 15% of pregnancies that are recognized clinically. Many causes can be attributed to the recurrent pregnancy loss e.g. chromosomal anomalies, thrombophilic disorders, uterine anomalies, endocrine abnormalities and fetal anomalies. Thrombophilia can be either hereditary or acquired. Multiple genes had been implicated in the pathogenesis of the thrombophilia. Previous studies have indicated that genetic polymorphism of the plasminogen activator inhibitor-1 gene (PAI-1) may be associated with recurrent abortion. Aim: The aim of the present study was to investigate whether plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism is associated with the occurrence of recurrent pregnancy loss or not. Methods: DNA samples were collected from sixty six female patients with recurrent abortion (33 primary abortion, 33 secondary abortion) and thirty four healthy controls with normal pregnancy for detection of plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism by restriction fragment length polymorphism PCR. Results: there was a significant association between PAI-1(-675 4G/5G) polymorphism and the occurrence of recurrent pregnancy loss. Conclusion: Our results assumed that PAI-1 (-675 4G/5G) polymorphism is associated with recurrent pregnancy loss.

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Genetic association of five plasminogen activator inhibitor-1 (PAI-1) polymorphisms and idiopathic recurrent pregnancy loss in Korean women

Thrombosis and Haemostasis ◽

10.1160/th13-03-0242 ◽

2013 ◽

Vol 110 (10) ◽

pp. 742-750 ◽

Cited By ~ 15

Author(s):

Bo Eun Lee ◽

Yi Seul Choi ◽

Ji Hyang Kim ◽

Ji Eun Shin ◽

HyungChul Rah ◽

...

Keyword(s):

Plasminogen Activator ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Plasminogen Activator Inhibitor ◽

Korean Women ◽

Plasminogen Activator Inhibitor 1 ◽

Ordinal Logistic Regression Analysis ◽

Polymerase Chain ◽

Activator Inhibitor ◽

Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1) is important for maintaining pregnancy. Aberrantly increased PAI-1 levels may contribute to thrombosis and inflammation, leading to pregnancy loss. This study investigated the association of PAI-1 polymorphisms (PAI-1 rs2227631 [-844G>A], rs1799889 [-675 4G/5G], rs6092 [43G>A], rs2227694 [9785G>A], and rs7242 [11053T>G]) with idiopathic recurrent pregnancy loss (RPL) in Korean women. We screened 308 RPL patients and 227 control participants for five PAI-1 polymorphisms. Genotyping of PAI-1 was performed by polymerase chain reaction-restriction fragment length polymorphism assay. PAI-1 4G4G and -844AA/ 4G4G/11053GG genotypes were associated with RPL. PAI-1 -844A/4G/43G/9785G/11053G haplotype was connected to hypofibrinolytic status (i.e. increased levels of plasma PAI-1, increased numbers of platelets, reduced prothrombin time, and reduced activated partial thromboplastin time). Moreover, PAI-1 11053TG+GG frequency was positively related to plasma homocysteine and urate levels, whereas -844AA frequency was associated with plasma folate concentrations according to ordinal logistic regression analysis. Based on these results, we propose that PAI-1 -844G>A, 4G/5G, and 11053T>G polymorphisms are markers of RPL.

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Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population

Journal of Medical Biochemistry ◽

10.2478/jomb-2019-0028 ◽

2019 ◽

Vol 0 (0) ◽

Author(s):

Ivana Joksic ◽

Zeljko Mikovic ◽

Dejan Filimonovic ◽

Jelena Munjas ◽

Natasa Karadzov Orlic ◽

...

Keyword(s):

Plasminogen Activator ◽

Gene Polymorphisms ◽

Factor Xiii ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

History Of ◽

Activator Inhibitor ◽

Pai 1

SummaryBackgroundRecurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls.MethodsThe study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays.ResultsOur results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15–6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11–17.46, P=0.044).ConclusionsThis is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

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Enoxaparin Effect on Pregnancy Outcomes in a Patient with Elevated Plasminogen Activator Inhibitor-1

Case Reports in Obstetrics and Gynecology ◽

10.1155/2020/7860324 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Kathleen Minor ◽

Heidi Leftwich

Keyword(s):

Plasminogen Activator ◽

Pregnancy Outcomes ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Plasminogen Activator Inhibitor ◽

Chronic Hypertension ◽

Plasminogen Activator Inhibitor 1 ◽

Adverse Pregnancy ◽

Activator Inhibitor ◽

Pai 1

Background. Plasminogen activator inhibitor-1 (PAI-1) inhibits tPA and creates a prothrombotic state. Gene polymorphisms of PAI-1 are associated with elevated levels and adverse pregnancy outcomes. Case. A 36-year-old gravida 6, para 1-1-3-1 with elevated prepregnancy PAI-1 levels, a history of early-onset preeclampsia with severe features superimposed on chronic hypertension, intrauterine growth restriction (IUGR), and recurrent pregnancy loss (RPL), presented with a dichorionic-diamniotic twin gestation. She was managed with aspirin and enoxaparin and delivered appropriately grown twins at 36 weeks and 3 days, due to the development of preeclampsia superimposed on chronic hypertension. She was discharged not on enoxaparin and represented with pulmonary edema on postoperative day 8. Conclusion. It is reasonable to consider testing certain patients with recurrent pregnancy loss and/or early preeclampsia with severe features for PAI-1. If levels are elevated, treatment with prophylactic enoxaparin may be beneficial. Further research is needed to determine the effect of this therapy in patients with exceedingly poor perinatal outcomes to better assess for any impact on improved outcomes.

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Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women

Journal of Personalized Medicine ◽

10.3390/jpm11121378 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1378

Author(s):

Hee Young Cho ◽

Han Sung Park ◽

Eun Hee Ahn ◽

Eun Ju Ko ◽

Hyeon Woo Park ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Plasminogen Activator Inhibitor ◽

Endocrine Disorders ◽

Plasminogen Activator Inhibitor 1 ◽

Tissue Plasminogen ◽

Activator Inhibitor ◽

Pai 1

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356–0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301–0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047–2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL.

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