Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.
Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.
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DOI：
10.1016/j.atherosclerosis.2011.01.038
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发表时间：
2011-05
期刊：
影响因子：
5.3
通讯作者：
Heiss, Gerardo
中科院分区：
文献类型：
--
作者：
Kucharska-Newton, Anna M.;Monda, Keri L.;Campbell, Stephen;Bradshaw, Patrick T.;Wagenknecht, Lynne E.;Boerwinkle, Eric;Wasserman, Bruce A.;Heiss, Gerardo
血小板的活化和聚集在心血管疾病的发病机制中起着重要作用。我们利用社区动脉粥样硬化风险（ARIC）颈动脉MRI研究的数据，研究了GPIIIa血小板糖蛋白（Leu33Pro）的单核苷酸多态性（SNP）与颈动脉斑块形态和血小板标志物表达的关系。研究样本包括2004-2005年ARIC研究队列中的1202名高加索人，他们参与了基于最大颈动脉壁厚度分层抽样的颈动脉MRI亚研究。在ITGB3基因中鉴定出Leu33Pro多态性为SNP rs5918。斑块可视化是通过增强MRI检查颈动脉最厚段完成的。采用空腹全血流式细胞术检测血小板标志物的表达。这项基于年龄和性别调整加权线性回归模型的横断面分析表明，Leu33Pro风险等位基因(C)的纯合子平均和最小纤维帽厚度降低。我们没有观察到不同SNP rs5918基因型的斑块脂质体积或最大颈动脉壁厚度的差异。与主要等位基因纯合子相比，Leu33Pro多态性携带者表达p -选择素（一种指示激活状态的血小板糖蛋白）的血小板比例更高。流行的冠心病不影响纤维帽厚度或血小板活化的估计。我们的研究结果表明，具有GPIIIa糖蛋白Leu33Pro多态性的个体可能倾向于增加动脉粥样硬化斑块破裂的风险。
Platelet activation and aggregation play an important role in the pathogenesis of cardiovascular disease. We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers using data from the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study. The study sample consisted of 1,202 Caucasian members of the ARIC study cohort recruited in 2004-2005 to participate in the Carotid MRI Substudy under stratified sampling based on maximum carotid artery wall thickness. The Leu33Pro polymorphism was identified as SNP rs5918 in the ITGB3 gene. Plaque visualization was accomplished with contrast enhanced MRI examination of the thickest segment of the carotid artery. Expression of platelet markers was measured using fasting whole blood flow cytometry. This cross-sectional analysis based on age and gender adjusted weighted linear regression models suggests that those homozygous for the Leu33Pro risk allele (C) have decreased mean and minimum fibrous cap thickness. We did not observe differences in plaque lipid volume or maximum carotid artery wall thickness across SNP rs5918 genotypes. Carriers of the Leu33Pro polymorphism, as compared to major allele homozygotes, had greater percent of platelets expressing P-selectin, a platelet glycoprotein indicating activation status. Prevalent coronary heart disease did not affect estimates of fibrous cap thickness or of platelet activation. Our results suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture.
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