Jiménez S, Tàssies D, Espinosa G, García-Criado A, Plaza J, Monteagudo J, Cervera R, Reverter J C
Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatologia, Hospital Clínic, Barcelona, Catalonia, Spain.
Ann Rheum Dis. 2008 Jun;67(6):835-40. doi: 10.1136/ard.2007.077321. Epub 2007 Aug 29.
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).
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.
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).
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.
我们分析了抗磷脂综合征（APS）或系统性红斑狼疮（SLE）患者血小板糖蛋白（GP）Ib-α、Ia/IIa和IIb/IIIa的基因多态性及其与动脉血栓形成和临床前期动脉硬化发展的相关性。
我们纳入了131例APS患者（86例原发性APS患者和45例与SLE相关的APS患者）、102例SLE患者和160名健康对照者。通过聚合酶链反应测定GP Ib-α可变数目串联重复序列（VNTR）多态性、GP Ia/IIa 807 C/T多态性和GP IIb/IIIa PlA1/2多态性。临床评估血栓形成事件，并通过客观方法进行确认。在70例SLE患者亚组中，通过颈动脉超声研究评估临床前期动脉硬化的存在情况，测量内膜中层壁厚度和动脉硬化斑块的存在情况。
已记录到36例APS患者共发生50次动脉血栓形成事件。我们发现GP Ia/IIa的807 T/T基因型与动脉血栓形成之间存在显著相关性（22%对7%，p = 0.04；比值比3.59，95%置信区间1.20至10.79）。单独分析时，VNTR Ib-α和P1A1/2 IIb/IIIa多态性与APS患者的动脉血栓形成无关。807 T和PlA2等位基因同时存在会增加动脉血栓形成风险（28%对7%，p = 0.005；比值比4.84，95%置信区间1.67至13.96）。在SLE患者中，未发现颈动脉动脉硬化斑块的存在与血小板GP的单独多态性之间存在关联。GP Ia/IIa的807 T等位基因和GP IIb/IIIa的PlA2等位基因同时存在与颈动脉斑块的存在相关（35%对4%，p = 0.002；比值比12.92，95%置信区间2.39至69.81）。
GP Ia/IIa的807 C/T多态性的T/T基因型可能是APS患者发生动脉血栓形成的额外风险因素。807 T和PlA2等位基因同时存在会增加APS患者的动脉血栓形成风险以及SLE患者临床前期动脉硬化的风险。
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