Plasminogen Activator Inhibitor-1 (SERPINE1) Genotyping

Last Literature Review: December 2020 Last Update:
  • Use to screen for genetic susceptibility for VTE or MI in individuals with a personal or family history of thrombotic events
  • Aids in risk/benefit assessment for preventive or therapeutic interventions for VTE or MI

The plasminogen activator inhibitor 1 (PAI-1) protein, which is encoded by the SERPINE1 gene, is involved in hemostasis, or the normal blood clotting pathway. The 4G/5G polymorphism in the promoter region of this gene is a major determinant of PAI-1 expression. Individuals who are heterozygous or homozygous for the 4G allele may have an increased risk for venous thromboembolism (VTE), especially when there are other risk factors for thrombophilia. , ,  This genotype may also confer an increased risk for myocardial infarction (MI). 

Genetics

Gene/Variants

The 4G/5G polymorphism is located at c.-817dupG (from start of translation) in the promoter region of the SERPINE1 gene.

Inheritance

Autosomal dominant

Frequency of the 4G allele varies by ethnicity:

  • White: 0.52
  • Hispanic: 0.38
  • African American: 0.13-0.28

Test Interpretation

Sensitivity/Specificity

Analytic sensitivity/specificity: 99%

Clinical sensitivity: unknown

Results

GenotypeAllele(s) detectedClinical significance
5G/5G genotype2 copies of 5G allele

Not at increased risk of VTE and MI

Does not exclude other genetic or nongenetic causes of thrombosis

4G/5G genotype1 copy of 4G alleleAssociated with increased risk of VTE and MI, particularly in individuals with other thrombotic risk factors
4G/4G genotype2 copies of 4G allele detected

Limitations

  • Variants other than the 4G/5G polymorphism in the SERPINE1 gene are not evaluated.
  • Test does not evaluate risk for complete PAI-1 deficiency.
  • Diagnostic errors can occur due to rare sequence variations.
Related Information
Venous Thromboembolism
Fibrinolytic Disorders
Hereditary Thrombophilia - Hypercoagulability