P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome.

Abstract

Antiphospholipid antibodies (aPLA) have been shown to enhance thrombus formation by increasing the expression of adhesive receptors such as P-selectin on endothelial cells. The P-selectin counter-receptor on leucocytes is P-selectin glycoprotein ligand-1 (PSGL-1). We have previously described a variable number of tandem repeats (VNTR) polymorphism in the mucin-like region of PSGL-1, with three alleles: allele A, 16 repeats; allele B, 15 repeats; and allele C, 14 repeats. We compared the PSGL-1 VNTR allele and genotype frequencies in 90 patients with antiphospholipid syndrome (APS) with thrombosis, 39 patients with persistent aPLA positivity without thrombosis, and 203 healthy controls. The frequency of the B allele was significantly higher in patients with APS with thrombosis compared with patients without thrombosis (p = 0.023). When we compared the groups by genotype frequencies, we found a markedly higher frequency of the AB genotype in patients with APS with thrombosis than in aPLA-positive patients without thrombosis (38.9% vs 10.3%, p = 0.001) or in normal population (38.9% vs 22.2%, p<0.01). We suggest that the VNTR polymorphism of PSGL-1 is a significant determinant of thrombotic predisposition in patients with APS. Furthermore, risk appears to correlate best with the combination of alleles inherited rather than with the presence of any particular allele.