Department of Hematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Blood. 2011 Jan 27;117(4):1393-9. doi: 10.1182/blood-2010-03-273961. Epub 2010 Oct 12.
High levels of von Willebrand factor (VWF) are associated with an increased risk for cardiovascular disease (CVD). Although VWF levels are strongly heritable and genetic susceptibility is an important risk factor for CVD, information on the contribution of common VWF gene variants to VWF levels and CVD risk is limited. In a case-control study of 421 young patients with a first event of acute coronary heart disease (CHD) or ischemic stroke (IS), and 409 healthy control participants (men aged ≤ 45 years, women aged ≤ 55 years), 27 haplotype-tagging single-nucleotide polymorphisms (ht-SNPs), covering the total common VWF gene variation, were selected and genotyped. The associations between these SNPs, VWF antigen (VWF:Ag) levels, VWF collagen-binding (VWF:CB) activity, and CVD risk was investigated. Two new associations were identified. For ht-SNP rs4764478 (intron 45), the increase in VWF:Ag levels and VWF:CB activity per minor allele was 0.082 (± 0.026) IU/mL (P = .001) and 0.096 (± 0.030) IU/mL (P = .002), respectively. ht-SNP rs216293 (intron 17) was associated with CVD risk (odds ratio, 1.44; 95% confidence interval [CI], 1.12-1.86 per minor allele). We confirmed the association between rs1063857 and CVD risk. Our data show that common variants in the VWF gene are associated with VWF levels and with the risk for CVD.
高水平的血管性血友病因子（VWF）与心血管疾病（CVD）的风险增加有关。尽管 VWF 水平具有很强的遗传性，遗传易感性是 CVD 的一个重要危险因素，但关于常见 VWF 基因变异对 VWF 水平和 CVD 风险的贡献的信息有限。在一项针对 421 名首次发生急性冠状动脉心脏病（CHD）或缺血性中风（IS）的年轻患者和 409 名健康对照参与者（年龄≤45 岁的男性，年龄≤55 岁的女性）的病例对照研究中，选择并对 27 个单核苷酸多态性（SNP）单体型标签（ht-SNPs）进行了基因分型，这些 ht-SNPs 覆盖了整个常见的 VWF 基因变异。研究了这些 SNP 与 VWF 抗原（VWF：Ag）水平、VWF 胶原结合（VWF：CB）活性和 CVD 风险之间的关系。发现了两个新的关联。对于 ht-SNP rs4764478（内含子 45），每个次要等位基因的 VWF：Ag 水平和 VWF：CB 活性的增加分别为 0.082（±0.026）IU/mL（P=0.001）和 0.096（±0.030）IU/mL（P=0.002）。ht-SNP rs216293（内含子 17）与 CVD 风险相关（每个次要等位基因的比值比，1.44；95%置信区间[CI]，1.12-1.86）。我们证实了 rs1063857 与 CVD 风险之间的关联。我们的数据表明，VWF 基因中的常见变异与 VWF 水平和 CVD 风险相关。
