Plasminogen activator inhibitor-1 levels and polymorphisms.
OBJECTIVE
To review the published evidence of a relationship between levels of plasminogen activator inhibitor-1 (PAI-1) or the 4G/5G polymorphism of the PAI-1 gene and the occurrence of venous thromboembolic disease.


METHODS
Review of the medical literature using computerized databases and a review of secondary sources identified through bibliographies.


RESULTS
Plasminogen activator inhibitor-1 is an important inhibitor of the fibrinolytic system, so it is biologically plausible that elevated levels could suppress fibrinolysis and result in an increased risk of thrombosis. Several small studies reported associations between PAI-1 levels and venous thromboembolism, some of which appear to be familial. Problems with these studies include variations in PAI-1 plasma levels due to circadian changes and the acute phase response, as well as alterations due to common comorbid disease states. More recent investigations have focused on genetic polymorphisms, particularly the 4G/5G insertion/deletion in the promoter region, affecting transcription rates. The relation of 4G/5G to venous thrombosis has been investigated primarily in case-control studies, which have produced inconsistent findings. Most studies, however, have reported higher PAI-1 plasma levels in individuals with 4G/4G.


CONCLUSIONS
The evidence regarding the relationship between an elevated PAI-1 plasma level or PAI-1 genetic polymorphism and the risk of venous thromboembolism is conflicting. There is insufficient information to recommend use of PAI-1 levels or genotype in evaluating thrombophilia.
Francis
Charles W
CW
Vascular Medicine Unit, University of Rochester School of Medicine & Dentistry, Rochester, NY 14642, USA. charles_francis@urmc.rocheser.edu
D001780:Blood Coagulation Tests; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D017410:Practice Guidelines as Topic; D013923:Thromboembolism / Q000097:blood / Q000150:complications / Q000235:genetics*; D019851:Thrombophilia / Q000175:diagnosis / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000150:complications / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1