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.
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 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-alpha 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.
Jiménez
S
S
Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatologia, Hospital Clínic, Barcelona, Catalonia, Spain.
Tàssies
D
D
Espinosa
G
G
García-Criado
A
A
Plaza
J
J
Monteagudo
J
J
Cervera
R
R
Reverter
J C
JC
D000328:Adult; D000704:Analysis of Variance; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000235:genetics; D014463:Ultrasonography
D039421:Integrin alpha2; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins