Objective: We analysed the genetic polymorphisms in platelet glycoproteins (GP) Ib-alpha, 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-alpha VNTR polymorphism, GP Ia/IIa 807 C/T polymorphism and GP IIb/IIIa PlA1/2 polymorphism were determined by PCR. Thrombotic events were assessed clinically and confirmed by objective methods. The presence of preclinical arteriosclerosis was evaluated by carotid ultrasound study in a subgroup of 70 SLE patients measuring the intima-media wall thickness (IMT) and the presence of arteriosclerotic plaque.
Results: A total of 50 episodes of arterial thrombosis in 36 APS patients 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, IC: 1.20-10.79). The VNTR Ib-alpha and P1A1/2 IIb/IIIa polymorphisms were not associated with arterial thrombosis in APS patients when individually analyzed. The coexistence of both 807 T and PlA2 alleles increased the arterial thrombosis risk (28% vs 7%, p= 0.005; OR 4.84, IC: 1.67-13.96). In SLE patients, 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, IC: 2.39-69.81).
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 APS patients and preclinical arteriosclerosis in SLE patients.
- antiphospholipid syndrome
- platelet glycoprotein
- systemic lupus erythematosus