Gene polymorphism of plasminogen activator inhibitor-1 is a risk factor of thrombosis in patients with antiphospholipid syndrome
L. Mukhametova, R. Aisina, T. Reshetnyak, L. Patrushev, K. Gershkovich (Moscow, Russia)
Time: 17:15 - 18:15
Objective: Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by thrombotic disorders and pregnancy loss in the presence of antiphospholipid antibodies. Impairment of fibrinolysis is associated with increased level of plasminogen activator inhibitor-1 (PAI-1). The aim of this work was to study the relationship between the 4G/5G polymorphism of PAI-1 gene and thrombotic manifestation in patients with APS.
Methods: It was studied 45 patients with APS (32 women, 13 man, mean ± SD age 35 ± 12 years, duration of disease 0.5 - 40 years), 18 had systemic lupus erythematosus and 27 - APS without autoimmune diseases. Anti-cardiolipin and anti-beta2-glycoprotein I antibodies were measured. All the thrombotic events were assessed clinically and confirmed by objective methods. PAI-1 4G/5G polymorphism genotyping was conducted by PCR method. Activity of PAI-1 was determined from residual activity of tPA added to plasma in excess, using conjugated method.
Results: 17 patients were high, 7 – moderate, 8 – low positive and 13 - negative by aCL, corresponding levels of aβ2GPI had 21, 4, 4 and 16 patients. The PAI-1 genotype 4G/4G had 21 (46.6%), 4G/5G - 18 (40%) and 5G/5G - 6 (13.4%) patients. Thrombosis had 39 (86.6%) patients: 9 (20%) - arterial, 21 (46.6%) – venous, 9 (20%) - combined thrombosis. Venous thrombosis had 14 (66.7%) with 4G/4G, 14 (77.7%) with 4G/5G and 2 (33.3%) with 5G/5G genotype, arterial thrombosis had 7 (33.3%), 6 (33.3%) и 5 (83.3%) patients, respectively. Increased level of active PAI-1 had 34 (75.5%) patients: 16 with 4G/4G, 13 – 4G/5G and 5 – 5G/5G genotype, normal PAI-1 activity had 11 (24.4%) patients: 5, 5 and 1, respectively. Relation between anti-cardiolipin and anti-beta2-glycoprotein I levels and thrombosis, level and polymorphism PAI-1 was not found. Combination of thrombosis, 4G/4G or 4G/5G genotype and increased activity of PAI-1 were observed in 34 (75.5%) patients with APS.
Conclusion: The results indicate on the relationship between 4G/5G polymorphism PAI-1 gene and thrombosis in patients with APS.