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Double heterozygosity polymorphisms for platelet glycoproteins Ia/IIa and IIb/IIIa increases arterial thrombosis and arteriosclerosis in patients with the antiphospholipid syndrome or with systemic lupus erythematosus
  1. S Jiménez1,
  2. D Tàssies2,
  3. G Espinosa1,
  4. Á García-Criado3,
  5. J Plaza1,
  6. J Monteagudo2,
  7. R Cervera1,
  8. J C Reverter2
  1. 1
    Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatologia, Hospital Clínic, Barcelona, Catalonia, Spain
  2. 2
    Department of Hemotherapy and Hemostasis, Centre de Diagnòstic Biomèdic, Hospital Clínic, Barcelona, Catalonia, Spain
  3. 3
    Department of Radiology, Centre de Diagnòstic per la Imatge, Hospital Clínic, Barcelona, Catalonia, Spain
  1. Ricard Cervera, Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatologia, Hospital Clínic, C/Villarroel 170, 08036 Barcelona, Catalonia, Spain; rcervera{at}clinic.ub.es

Abstract

Objective: We analysed the genetic polymorphisms in platelet glycoproteins (GP) Ib-α, Ia/IIa and IIb/IIIa and their correlation with the development of arterial thrombosis and preclinical arteriosclerosis in patients with antiphospholipid syndrome (APS) or with systemic lupus erythematosus (SLE).

Methods: We included 131 patients with APS (86 with primary APS and 45 with APS associated with SLE), 102 patients with SLE and 160 healthy controls. GP Ib-α VNTR polymorphism, GP Ia/IIa 807 C/T polymorphism and GP IIb/IIIa PlA1/2 polymorphism were determined by polymerase chain reaction. Thrombotic events were assessed clinically and confirmed by objective methods. The presence of preclinical arteriosclerosis was evaluated by a carotid ultrasound study in a subgroup of 70 patients with SLE measuring the intima-media wall thickness and the presence of arteriosclerotic plaque.

Results: A total of 50 episodes of arterial thrombosis in 36 patients with APS have been registered. We found a significant correlation between the 807 T/T genotype of GP Ia/IIa and arterial thrombosis (22% vs 7%, p = 0.04; OR 3.59, 95% CI 1.20 to 10.79). The VNTR Ib-α and P1A1/2 IIb/IIIa polymorphisms were not associated with arterial thrombosis in patients with APS when individually analysed. The coexistence of both 807 T and PlA2 alleles increased the arterial thrombosis risk (28% vs 7%, p = 0.005; OR 4.84, 95% CI 1.67 to 13.96). In patients with SLE, no relationship was found between the presence of carotid arteriosclerotic plaque and separate polymorphisms of platelet GP. The coexistence of alleles 807 T of GP Ia/IIa and PlA2 of GP IIb/IIIa was associated with the presence of carotid plaque (35% vs 4%, p = 0.002; OR 12.92, 95% CI 2.39 to 69.81).

Conclusions: The T/T genotype of 807 C/T polymorphism of GP Ia/IIa may be an additional risk for the development of arterial thrombosis in APS. The coexistence of both 807 T and PlA2 alleles increased the arterial thrombosis risk in patients with APS and preclinical arteriosclerosis in patients with SLE.

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Footnotes

  • Funding: Supported in part by grants FIS 2000/1048, FIS 2002/0696, FIS 2002/0711 and FIS 2003/0280 from Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III, Spanish Ministry of Health) of Spain.

  • Competing interests: None.

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