The 4G/5G polymorphism of the type 1 plasminogen activator-inhibitor gene and thrombosis in patients with antiphospholipid syndrome

Objective. To investigate the relationship between the 4G/5G polymorphism o f the type 1 plasminogen activator inhibitor (PAI-1) gene and thrombotic ma nifestations in patients with antiphospholipid syndrome (APS), Methods. We studied a total of 247 patients included in the following 4 gro ups: 70 patients with primary APS, 104 patients with systemic lupus erythem atosus (40 with antiphospholipid antibodies [aPL] and clinical [secondary] APS, 13 with aPL but without clinical APS, and 51 with neither detectable a PL nor a history of thrombosis), 14 asymptomatic individuals with aPL, and 59 patients with thrombosis but without known thrombosis risk factors. A co ntrol group of 100 healthy individuals was also analyzed. PAI-1 4G/5G polym orphism was determined by polymerase chain reaction and endonuclease digest ion. Results. The allele frequency of 4G/5G in controls was 0.47/0.53. There wer e no differences in allele distribution among patient groups or between pat ients and controls. However, a higher frequency of the 4G allele was observ ed 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 fr equency in patients with versus those without arterial thrombosis (0.64 ver sus 0.43; P < 0.01) (OR 5.96, 95% CI 1.67-21.32), while patients with venou s thrombosis had an allele distribution similar to that of those without ve nous thrombosis (0.49 versus 0.50; P not significant). There was a trend to ward 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.