Mello Tayana B T, Siqueira Lúcia H, Montavão Silmara A L, Ozello Margarete C, Annichino-Bizzacchi Joyce M
Hematology and Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
Thromb Res. 2008;121(5):625-9. doi: 10.1016/j.thromres.2007.08.002. Epub 2007 Sep 21.
Low-density lipoprotein receptor-related protein is a receptor involved in factor VIII catabolism. In spite of elevated factor VIII coagulant activity levels being a well-established independent risk factor for venous thrombosis, the origin of this abnormality is unknown. In this study, we investigated the role of polymorphisms C220T (exon 22), A775P (exon 14) and D2080N (exon 39) in the gene coding for this receptor in 249 patients (100 males/149 female, mean age 36.5 SD:11 years) with venous thromboembolism and 366 controls (155 male/211 females, mean age 38 SD:11 years ) matched by age and gender. The polymorphisms C220T (CT OR: 0.9, 95%CI: 0.6-1.2; TT OR: 1.0, 95%CI: 0.6-1.5) and D2080N (OR: 0.8, 95%CI: 0.3-2.4) were not associated to thrombosis susceptibility while the polymorphism A775P was identified in neither patients or controls. D2080N polymorphism was associated with factor VIII and von Willebrand factor levels, in the control group. Heterozygous individuals (DN), compared with homozygotes individuals (DD), presented lower levels of factor VIII (mean difference: 42.3 IU/dL, 95%CI: 5.7-78.9) and von Willebrand factor (mean difference: 34.8 IU/dL, 95%CI: 4.9-64.6). In conclusion, we demonstrated an association between D2080N polymorphism with factor VIII and von Willebrand factor levels in Brazilian normal individuals. However, none of the three polymorphisms in low-density lipoprotein receptor related protein gene were related to venous thrombosis risk in these patients.
低密度脂蛋白受体相关蛋白是一种参与凝血因子VIII分解代谢的受体。尽管凝血因子VIII促凝活性水平升高是静脉血栓形成公认的独立危险因素，但这种异常的起源尚不清楚。在本研究中，我们调查了编码该受体的基因中C220T（第22外显子）、A775P（第14外显子）和D2080N（第39外显子）多态性在249例静脉血栓栓塞患者（100例男性/149例女性，平均年龄36.5岁，标准差：11岁）和366例按年龄和性别匹配的对照组（155例男性/211例女性，平均年龄38岁，标准差：11岁）中的作用。多态性C220T（CT比值比：0.9，95%置信区间：0.6-1.2；TT比值比：1.0，95%置信区间：0.6-1.5）和D2080N（比值比：0.8，95%置信区间：0.3-2.4）与血栓形成易感性无关，而多态性A775P在患者和对照组中均未被发现。在对照组中，D2080N多态性与凝血因子VIII和血管性血友病因子水平相关。杂合子个体（DN）与纯合子个体（DD）相比，凝血因子VIII水平较低（平均差异：42.3 IU/dL，95%置信区间：5.7-78.9），血管性血友病因子水平较低（平均差异：34.8 IU/dL，95%置信区间：4.9-64.6）。总之，我们证明了巴西正常个体中D2080N多态性与凝血因子VIII和血管性血友病因子水平之间存在关联。然而，低密度脂蛋白受体相关蛋白基因中的这三种多态性均与这些患者的静脉血栓形成风险无关。
