Genetics of platelet reactivity in normal, healthy individuals
Genetics of platelet reactivity in normal, healthy individuals
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DOI：
10.1111/j.1538-7836.2009.03610.x
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发表时间：
2009-12-01
影响因子：
10.4
通讯作者：
Nugent, D. J.
中科院分区：
文献类型：
--
作者：
Kunicki, T. J.;Williams, S. A.;Nugent, D. J.
背景：血小板功能分析仪-100（PFA-100）被广泛用于在高剪切下测量全血中的血小板反应性。目的：利用PFA-100分析正常人血小板反应性的遗传成分。研究方法：我们比较了基线血小板反应性与性别、年龄、血小板计数、红细胞压积、血浆血管性血友病因子抗原（VWF：Ag）和7个候选基因的等位基因：整合素亚基α 2（ITGA 2）和β 3（ITGB 3）、血小板糖蛋白GPIb α（GP 1BA）和GPVI（GP 6）、嘌呤受体（P2 RY 1和P2 RY 12）和环氧合酶-1（COX 1）。结果如下：基于线性和逻辑回归模型，我们报告了胶原蛋白加肾上腺素（CEPI）启动的基线闭合时间（CT）与血浆VWF：Ag水平、ITGA 2 807 T和P2 RY 1 893 C之间的负相关性，以及胶原蛋白加二磷酸腺苷（CADP）启动的基线CT与P2 RY 1 893 C或GP 1BA-5C之间的负相关性。结论：这些结果表明，ITGA 2和P2 RY 1的遗传多态性联合收割机与血浆VWF：Ag水平相结合，调节血小板对胶原蛋白加EPI的反应性，而P2 RY 1和GP 1BA的遗传差异显著影响血小板对胶原蛋白加ADP的反应性。我们的研究结果表明，PFA-100可用于评估血小板功能的遗传预测因子的影响。
Background: The Platelet Function Analyzer-100 (PFA-100) is widely used to measure platelet reactivity in whole blood under high shear. Objective: To characterize the genetic component of platelet reactivity among normal individuals, using the PFA-100. Methods: We compared baseline platelet reactivity with sex, age, platelet count, hematocrit, plasma von Willebrand factor antigen (VWF:Ag), and alleles of seven candidate genes: integrin subunits alpha 2 (ITGA2) and beta 3 (ITGB3), platelet glycoproteins GPIb alpha (GP1BA) and GPVI (GP6), purinogenic receptors (P2RY1 and P2RY12) and cyclooxygenase-1 (COX1). Results: Based on linear and logistic regression models, we report an inverse correlation between baseline closure time (CT) initiated by collagen plus epinephrine (CEPI) and plasma VWF:Ag level, ITGA2 807T and P2RY1 893C, and an inverse correlation between baseline CT initiated by collagen plus adenosine diphosphate (CADP) and P2RY1 893C or GP1BA -5C. Conclusions: These results indicate that genetic polymorphisms in ITGA2 and P2RY1 combine with plasma VWF:Ag levels to modulate baseline platelet reactivity in response to collagen plus EPI, while genetic differences in P2RY1 and GP1BA significantly effect platelet responses to collagen plus ADP. Our results demonstrate that the PFA-100 can be used to evaluate the effects of genetic predictors of platelet function.