Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor
Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor
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DOI：
10.1182/blood-2009-10-249102
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发表时间：
2010-07-15
期刊：
影响因子：
20.3
通讯作者：
Montgomery, Robert R.
中科院分区：
文献类型：
--
作者：
Flood, Veronica H.;Gill, Joan Cox;Montgomery, Robert R.
血管性血友病的诊断依赖于血管性血友病因子（VWF）的特异性检测异常，包括VWF抗原（VWF: Ag）和VWF阻遏素辅助因子活性（VWF: RCo）。在检查参加T. S. Zimmerman项目的血管性血液病分子和临床生物学项目的健康对照组时，我们和其他人一样，发现非裔美国人对照组的VWF: RCo平均值比VWF: Ag低，因此寻找这些差异的遗传原因。在非裔美国人对照中，3外显子28单核苷酸多态性（snp） I1380V、N1435S和D1472H的存在与VWF: RCo/VWF:Ag比值显著降低相关，而在非裔美国人和高加索人对照中，D1472H的存在与该比值降低相关。多因素分析比较了种族、SNP状态和VWF: RCo/VWF: Ag比值，证实只有D1472H的存在是显著的。无论SNP状态如何，VWF与胶原蛋白的结合均无差异。同样，使用独立于瑞斯托司汀的GPIb复合物结合试验也没有发现活性差异。由于VWF: RCo测定依赖于利斯托司汀与VWF的结合，VWF的突变（和多态性）可能会影响该测定对“VWF活性”的测量，并且可能不能反映功能缺陷或真正的出血风险。[血液。2010;116(2):280-286]
The diagnosis of von Willebrand disease relies on abnormalities in specific tests of von Willebrand factor (VWF), including VWF antigen (VWF: Ag) and VWF ristocetin cofactor activity (VWF: RCo). When examining healthy controls enrolled in the T. S. Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease, we, like others, found a lower mean VWF: RCo compared with VWF: Ag in African American controls and therefore sought a genetic cause for these differences. For the African American controls, the presence of 3 exon 28 single nucleotide polymorphisms (SNPs), I1380V, N1435S, and D1472H, was associated with a significantly lower VWF: RCo/VWF:Ag ratio, whereas the presence of D1472H alone was associated with a decreased ratio in both African American and Caucasian controls. Multivariate analysis comparing race, SNP status, and VWF: RCo/VWF: Ag ratio confirmed that only the presence of D1472H was significant. No difference was seen in VWF binding to collagen, regardless of SNP status. Similarly, no difference in activity was seen using a GPIb complex-binding assay that is independent of ristocetin. Because the VWF: RCo assay depends on ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of "VWF activity" by this assay and may not reflect a functional defect or true hemorrhagic risk. (Blood. 2010; 116(2): 280-286)