Article Text

PDF
P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome
  1. Reyhan Diz-Kucukkaya1,
  2. Murat Inanc2,
  3. Vahid Afshar-Kharghan3,
  4. Q Ed Zhang4,
  5. José A López5,
  6. Yuksel Pekcelen1
  1. 1
    Division of Hematology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  2. 2
    Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  3. 3
    Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
  4. 4
    Pre-Award Research Office, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
  5. 5
    Puget Sound Blood Center, University of Washington School of Medicine, Seattle, Washington, USA
  1. Reyhan Diz-Kucukkaya, MD, Mesa Yamacevler Sitesi, Akasya 5 blok, D6, Gokturk, 34490, Istanbul-Turkey; rkucukkaya{at}hotmail.com

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

  • antiphospholipid syndrome
  • P-selectin
  • P-selectin glycoprotein ligand-1
  • PSGL-1 VNTR polymorphism
  • thrombosis

Statistics from Altmetric.com

Footnotes

  • This work was supported by the Research Fund of the Istanbul University (Project number: T-967/19022001), TUBA-GEBIP (R.D.K./TUBA-GEBIP/2004-15), and by a grant from National Institutes of Health of the United States (Grant number RO1HL65205).

  • Competing interests: None declared.

  • Abbreviations:
    aPLA
    antiphospholipid antibodies
    APS
    antiphospholipid syndrome
    PSGL-1
    P-selectin glycoprotein ligand-1
    VNTR
    variable number of tandem repeats

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.