Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease

Thromb Haemost. 1999 Apr;81(4):516-21.


Increased circulating levels of type 1 plasminogen activator inhibitor (PAI-1) have been associated with coronary artery disease (CAD). However, genetic and environmental determinants of PAI-1 expression are only partially understood. The levels of PAI-1 have been found to relate to 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene. The 4G allele in this polymorphism has been associated with higher levels of plasma PAI-1 activity, but despite the strong correlation between PAI-1 activity and antigen, no association has been found between PAI-1 antigen levels and the PAI-1 promoter 4G/5G genotype. The aim of the present study was to analyze the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels in post-menopause women with coronary disease in comparison with healthy women in pre and postmenopausal status, and the influence of this genotype on variations in PAI-1 levels after hormone replacement therapy (HRT). No differences between 4G/5G allele distribution in the groups studied were observed. The group of postmenopausal women with CAD showed significantly increased PAI-1 antigen and activity levels in comparison with the control groups, and the levels of PAI-1 correlated with the 4G/5G genotype. A multivariate analysis revealed that in the CAD group there was a high correlation between 4G allele dosage and PAI-1 antigen levels, which were also influenced by the triglyceride levels but not by estrogen or glucose levels. After hormone replacement therapy the decrease in PAI-1 levels was correlated with the 4G allele dosage. We conclude that in the group of postmenopausal women with CAD the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels is more evident than in the control groups, and that the decrease in PAI-1 levels after HRT in CAD women correlates with the 4G allele dosage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens / blood
  • Blood Glucose / analysis
  • Cholesterol / blood
  • Coronary Disease / blood*
  • Estrogens / blood
  • Female
  • Genotype
  • Hormone Replacement Therapy
  • Humans
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Plasminogen Activator Inhibitor 1 / blood*
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Plasminogen Activator Inhibitor 1 / immunology
  • Postmenopause / blood*
  • Promoter Regions, Genetic
  • Triglycerides / blood


  • Antigens
  • Blood Glucose
  • Estrogens
  • Plasminogen Activator Inhibitor 1
  • Triglycerides
  • Cholesterol