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

Genotype Allele(s) detected Clinical significance

5G/5G genotype

2 copies of 5G allele

Not at increased risk of VTE and MI

Does not exclude other genetic or nongenetic causes of thrombosis

4G/5G genotype

1 copy of 4G allele

Associated with increased risk of VTE and MI, particularly in individuals with other thrombotic risk factors

4G/4G genotype

2 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