Plasminogen Activator Inhibitor 1 Gene Polymorphism and Gestational Diabetes Mellitus

Background: A number of processes regulating the thrombolytic balance are impaired in diabetic patients as a result of dysfunction of endothelial cells leading to a hypercoagulative state. Von Willebrand factor (VWF) is an important marker of endothelial dysfunction. Plasminogen activator inhibitor-1 antigen (PAI-1-Ag), the major physiological inhibitor of tissue plasminogen activator (tPA), is mainly produced by endothelium. The aim of this study is to measure plasma levels of von Willebrand factor, Plasminogen activator inhibitor-1 antigen in type 2 diabetes mellitus patients and to correlate with glycated haemoglobin (HbA1c). Study Design: This prospective cohort study was conducted on 30 diagnosed type 2 DM patients who were about to start treatment. Place and Duration of Study: Medical outpatient (MOP) clinic of Enugu State University of Science and Technology Teaching Hospital (ESUTTH), between January and December 2016. Methodology: We included 30 patients (13 men, 17 women; age range 40-80 years) with type 2 diabetes mellitus. Blood samples were drawn from the patients before they commenced treatment, six months into the treatment and at twelve months of the treatment. Blood samples were also drawn from 25 age matched non diabetic patients. Plasma von Willebrand factor and Plasminogen activator inhibitor-1 antigen levels were determined by Enzyme linked immunosorbent assay. Glycated haemoglobin (HbA1c) and fasting blood sugar (FBS) levels were also evaluated along with them. Results: This study was conducted on 30 type 2 DM patients consisting of 13 males and 17 females. At treatment naïve, mean levels of vWF were significantly increased (45.48 +/- 6.46) in male type 2 Diabetic patients compared to the control (20.45 +/- 0.26). Six months into treatment mean levels of vWF were significantly increased (48.18 +/- 4.99) in female type 2 Diabetic patients compared to the control (37.64 +/- 7.93). The plasma levels of vWF were significantly and positively correlated with HbA1c at six months into treatment in male type 2 DM patients. The plasma levels of vWF were also significantly and positively correlated with PAI-1 at six and twelve months into treatment in both genders. Conclusion: There was strong significant positive correlation between plasma levels of vWF and PAI-1 in type 2 diabetes mellitus patients.

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

Hematology & Transfusion International Journal ◽

10.15406/htij.2018.07.00203 ◽

2019 ◽

Vol 7 (2) ◽

pp. 41-44

Author(s):

Iglal Youssef Shaala ◽

Akram Abdel Moneim Deghady ◽

Reham Abdel Haleem Abo Elwafa ◽

Tamer Ahmed Hosny ◽

Engy Taher Ammar

Keyword(s):

Gene Polymorphism ◽

Plasminogen Activator ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Plasminogen Activator Inhibitor ◽

Recurrent Abortion ◽

Plasminogen Activator Inhibitor 1 ◽

Uterine Anomalies ◽

Activator Inhibitor ◽

Pai 1

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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Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-019-0018-1 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Fatma A. Khalaf ◽

Hatem R. Ibrahim ◽

Hanan M. Bedair ◽

Maha M. Allam ◽

Amr A. Elshormilisy ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gene Polymorphism ◽

Vascular Complications ◽

Plasminogen Activator Inhibitor ◽

Diabetic Patients ◽

Plasminogen Activator Inhibitor 1 ◽

Increased Risk ◽

Activator Inhibitor ◽

Pai 1

Abstract Background Diabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count, d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR). Results The most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. The d-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients. Conclusion This study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.

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The Relationship Between Plasminogen Activator Inhibitor-1 (PAI-1) A15T Gene Polymorphism And Prognosis Of Pulmonary Adenocarcinoma In Korean Population

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5148 ◽

2011 ◽

Author(s):

Ju Eun Lim ◽

Young Ae Kang ◽

Moo Suk Park

Keyword(s):

Gene Polymorphism ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Pulmonary Adenocarcinoma ◽

Korean Population ◽

Plasminogen Activator Inhibitor 1 ◽

The Relationship ◽

Activator Inhibitor ◽

Pai 1

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Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus?

Journal of Laboratory Physicians ◽

10.4103/0974-2727.180790 ◽

2016 ◽

Vol 8 (02) ◽

pp. 101-105 ◽

Cited By ~ 5

Author(s):

Suheyla Gorar ◽

Bulent Alioglu ◽

Esranur Ademoglu ◽

Seyit Uyar ◽

Handan Bekdemir ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Study Groups ◽

Tissue Type ◽

Coagulation System ◽

Significant Difference ◽

Pai 1

ABSTRACT Context: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. Aims: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. Settings and Design: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. Subjects and Methods: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. Statistical Analysis Used: One-way analysis of variance, Kruskal–Wallis, and post hoc Tukey honestly significant difference or Conover’s nonparametric multiple comparison tests for comparison of the study groups. Results: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. Conclusions: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis.

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