Increase in plasma plasminogen activators inhibitor type 1 concentration after fibrinolytic treatment in patients with acute myocardial infarction is associated with 4G/5G polymorphism of PAI-1 gene

J Thromb Haemost. 2006 Jun;4(6):1361-6. doi: 10.1111/j.1538-7836.2006.01990.x.

Abstract

Background: Preliminary data suggest that plasma concentration of plasminogen activators inhibitor type 1 (PAI-1) is genetically determined and may be related to differential regulation of plasma PAI-1 concentration at baseline and after stimulation.

Aim: This study aimed to evaluate whether increase in the plasma PAI-1 antigen concentration or activity after fibrinolytic therapy in patients with acute myocardial infarction is associated with the -675 4G/5G genetic polymorphism in the promoter region of PAI-1 gene.

Results & conclusions: Our study revealed that a rebound effect is observed in PAI-1 activity (ActPAI-1) and PAI-1 antigen (AgPAI-1) concentration after standard streptokinase treatment with maximal values of 3 h (t3) after the completion of streptokinase infusion. Both ActPAI-1 and AgPAI-1 were significantly higher at t3 compared to the levels before fibrinolytic treatment: 37.3 (20.0-67.7) vs. 10.0 (3.6-26.0) IU L(-1); P = 0.00001 and 29.9 (15.6-42.3) vs. 20.9 (13.0-30.2) ng mL(-1); P = 0.001, respectively. The stratification of the patients by genotype revealed that carriers of the 4G allele had higher concentrations of PAI-1 antigen 3 h after streptokinase infusion: 30.9 vs. 13.8 ng mL(-1); P = 0.019. No significant association between PAI-1 activity and genotype was found. In conclusion, the rebound effect in serum PAI-1 concentration observed after streptokinase treatment may be related to the 4G/5G polymorphism in the PAI-1 gene promoter.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics
  • Streptokinase / therapeutic use*
  • Thrombolytic Therapy*

Substances

  • Fibrinolytic Agents
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Streptokinase