Objectives: Antiphospholipid antibodies (aPLA) have been shown to enhance thrombus formation by increasing the expression of adhesive receptors on endothelial cells including P-selectin. The P-selectin counter-receptor on leukocytes 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.
Methods: We compared the PSGL-1 VNTR allele and genotype frequencies in 90 antiphospholipid syndrome (APS) patients with thrombosis, 39 patients with persistent aPLA-positivity and without thrombosis, and 203 healthy controls.
Results: The frequency of the B allele was significantly higher in APS patients with thrombosis compared to 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 APS patients with thrombosis than in aPL-positive patients without thrombosis (38.9% versus 10.3%, p=0.001) or in normal population (38.9% versus 22.2%, p=0.0048).
Conclusions: We suggest that the VNTR polymorphism of PSGL-1 is a significant determinant of the thrombotic predisposition of patients with APS. Further, risk appears to correlate best with the combination of alleles inherited rather than the presence of any particular allele.
- PSGL-1 VNTR polymorphism
- antiphospholipid syndrome
- p-selectin glycoprotein ligand-1