Investigation of association between plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G polymorphism frequency and plasma PAI-1 enzyme activity in patients with acute stroke

Genet Test. 2008 Sep;12(3):443-51. doi: 10.1089/gte.2008.0025.

Abstract

Aim: This study was carried out to determine if there is any association between plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G polymorphism and plasma PAI-1 enzyme activity in acute stroke patients.

Methods: In this study, 333 genomic DNAs (from 253 acute stroke patients and 80 healthy subjects) were analyzed. Genomic DNAs were prepared from peripheral blood using a saline method. These DNAs were amplified by PCR method using primers specific for 4G and 5G alleles. PCR products were separated by 2% agarose gel electrophoresis and visualized by a charge coupled device (CCD) camera. PAI-1 enzyme activities were measured by ELISA method. The results were evaluated statistically with Student's t-test, chi(2)-test, one-way analysis of variance, and stepwise regression analysis.

Results: In this study, frequency of PAI-1 gene 4G5G genotype was found to be low both in patients and controls. PAI-1 enzyme activities were significantly increased in acute stroke patients compared to controls. Although PAI-1 gene 4G5G genotype frequencies were low, the patients carrying this allele had highest plasma PAI-1 enzyme activity; likewise, although PAI-1 gene 4G4G genotype frequencies were high, the patients carrying this allele had lowest plasma PAI-1 enzyme activities. Homocysteine levels had a positive effect of 65% on plasma PAI-1 enzyme activities.

Conclusion: Consequently, in this study, we may assert that PAI-1 gene, 4G4G and 5G5G genotypes, PAI-1 activity, and homocysteine level determination are significant criteria for identifying patients who are likely to develop stroke; on the other hand, a direct relation does not exist between gene polymorphism and enzyme activity.

MeSH terms

  • Alleles
  • Case-Control Studies
  • Female
  • Gene Frequency*
  • Humans
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Stroke / genetics*
  • Tissue Plasminogen Activator / genetics*

Substances

  • Plasminogen Activator Inhibitor 1
  • Tissue Plasminogen Activator