scholarly journals Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zaid Al-Hamodi ◽  
Riyadh Saif-Ali ◽  
Ikram S. Ismail ◽  
Khaled A. Ahmed ◽  
Sekaran Muniandy

Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35,P=0.045;OR=1.67,P=0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32,P=0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

2019 ◽  
Vol 9 (7) ◽  
pp. 484
Author(s):  
Mehrnaz Imani ◽  
Soghra Rabizadeh ◽  
Manouchehr Nakhjavani ◽  
Payam Hashemi ◽  
Shaghayegh Pezeshki ◽  
...  

Background: Women with type 2 diabetes are more susceptible to coagulopathy disorders and endothelial dysfunction. One possible explanation is the effects of different sex hormones in inflammatory conditions. Increased plasminogen activator inhibitor-1 (PAI-1) activity has been observed as a possible predisposing factor for coagulopathy disorders and endothelial dysfunction. However, the effect of gender on PAI-1 in patients with type 2 diabetes (T2D) and albuminuria has not been studied sufficiently.Objectives: In this study, we examined whether changes of PAI-1 activity according to the albuminuria state in patients with type 2 diabetes are different in males and females.Materials and Methods: A matched case-control study was performed among participants with T2D, as 38 microalbuminuric patients were matched with 38 normoalbuminuric patients who were similar in age and body mass index (BMI). PAI-1 activity was compared between the two groups with and without gender stratification.Results: PAI-1 activity in microalbuminuric women was higher in comparison to that of the normoalbuminuric controls (P-value < 0.05). There was no significant difference in PAI-1 activity between macroalbuminuric and normoalbuminuric men. In women with type 2 diabetes and albuminuria, PAI-1 activity was independently and significantly associated with urinary albumin excretion.Conclusions: Gender differences in PAI-1 activity, seen in the early stages of diabetic nephropathy, are a possible explanation for the higher incidence of vasculopathy in women with type 2 diabetesKeywords: plasminogen activator inhibitor-1; coagulopathy; microalbuminuria; type 2 diabetes; gender


1990 ◽  
Vol 265 (1) ◽  
pp. 109-113 ◽  
Author(s):  
T L Lindahl ◽  
P I Ohlsson ◽  
B Wiman

The structural events taking place during the reaction between PAI-1 (plasminogen-activator inhibitor 1) and the plasminogen activators sc-tPA (single-chain tissue plasminogen activator) and tc-tPA (two-chain tissue plasminogen activator) were studied. Complexes were formed by mixing sc-tPA or tc-tPA with PAI-1 in slight excess (on an activity basis). The complexes were purified from excess PAI-1 by affinity chromatography on fibrin-Sepharose. Examination of the purified complexes by SDS/polyacrylamide-gel electrophoresis (SDS/PAGE) and N-terminal amino acid sequence analysis demonstrated that a stoichiometric 1:1 complex is formed between PAI-1 and both forms of tPA. Data obtained from both complexes revealed the amino acid sequences of the parent molecules and, in addition, a new sequence: Met-Ala-Pro-Glu-Glu-. This sequence is found in the C-terminal portion of the intact PAI-1 molecule and thus locates the reactive centre of PAI-1 to Arg346-Met347. The proteolytic activity of sc-tPA is demonstrated by its capacity to cleave the ‘bait’ peptide bond in PAI-1. The complexes were inactive and dissociated slowly at physiological pH and ionic strength, but rapidly in aq. NH3 (0.1 mol/l). Amidolytic tPA activity was generated on dissociation of the complexes, corresponding to 0.4 mol of tPA/mol of complex. SDS/PAGE of the dissociated complexes indicated a small decrease in the molecular mass of PAI-1, in agreement with proteolytic cleavage of the ‘bait’ peptide bond during complex-formation.


Author(s):  
Ifeanyichukwu Martin Ositadinma ◽  
Ngwu Amauche Martina ◽  
Eluke Blessing Chekwube

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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