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P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome
  1. Reyhan Diz-Kucukkaya (rkucukkaya{at}hotmail.com)
  1. Istanbul University, Istanbul Faculty of Medicine, Turkey
    1. Murat Inanc (minanc{at}superonline.com)
    1. Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Rheumatology, Turkey
      1. Vahid Afshar-Kharghan (vahid{at}bcm.tmc.edu)
      1. Baylor College of Medicine, United States
        1. Q Ed Zhang
        1. Baylor College of Medicine, United States
          1. José López (josel{at}psbc.org)
          1. Puget Sound Blood Center, University of Washington School of Medicine, United States
            1. Yuksel Pekcelen
            1. Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Hematology, Turkey

              Abstract

              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
              • p-selectin glycoprotein ligand-1
              • thrombosis

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