Objective: To investigate the relationship between the 4G/5G polymorphism of the type 1 plasminogen activator inhibitor (PAI-1) gene and thrombotic manifestations in patients with antiphospholipid syndrome (APS).
Methods: We studied a total of 247 patients included in the following 4 groups: 70 patients with primary APS, 104 patients with systemic lupus erythematosus (40 with antiphospholipid antibodies [aPL] and clinical [secondary] APS, 13 with aPL but without clinical APS, and 51 with neither detectable aPL nor a history of thrombosis), 14 asymptomatic individuals with aPL, and 59 patients with thrombosis but without known thrombosis risk factors. A control group of 100 healthy individuals was also analyzed. PAI-1 4G/5G polymorphism was determined by polymerase chain reaction and endonuclease digestion.
Results: The allele frequency of 4G/5G in controls was 0.47/0.53. There were no differences in allele distribution among patient groups or between patients and controls. However, a higher frequency of the 4G allele was observed in APS patients with versus those without thrombosis (0.57 versus 0.39; P < 0.05) (odds ratio [OR] 2.83, 95% confidence interval [95% CI] 1.18-6.76). This higher frequency of the 4G allele was attributable to the higher frequency in patients with versus those without arterial thrombosis (0.64 versus 0.43; P < 0.01) (OR 5.96, 95% CI 1.67-21.32), while patients with venous thrombosis had an allele distribution similar to that of those without venous thrombosis (0.49 versus 0.50; P not significant). There was a trend toward higher PAI-1 antigen and activity levels in APS patients and controls with the 4G/4G genotype, but this did not reach statistical significance.
Conclusion: The presence of the 4G allele of the 4G/5G polymorphism of the PAI-1 gene may be an additional risk factor for the development of arterial thrombosis in APS.