Institute of Clinical Chemistry, Univ. Hospital Kiel & Lübeck, Germany.
University of Alberta, Edmonton, Canada.
Blood Cells Mol Dis. 2017 Sep;67:54-58. doi: 10.1016/j.bcmd.2016.12.012. Epub 2016 Dec 30.
Given the qualitative differences in the role of VKORC1 and CYP2C9 polymorphisms in Vitamin K antagonists (VKA) dosing variation between adults and children, we were interested in determining at what age these polymorphism begin to play a more significant role.
A prospective cohort study of 190 patients aged 1-86years receiving VKA for treatment of venous thromboembolism. Blood samples were collected beyond the acute thrombotic event when patients were on stable targeted INR (2-3) for plasma testing and VKORC1/CYP2C9 genotyping. Patient demographics including VKA dose were collected. Simple and multiple linear regression was used to assess the relationship of VKA dose with polymorphisms and weight, adjusted for quality of anticoagulation (INR, D-Dimer), liver (AST, ALT) and renal function.
In subjects 1-19years of age, weight explained 39.0% of dosing variation with VKORC1 and CYP2C9 playing a minor role. In contrast, in subjects 20-40years weight contributed 23%, VKORC1 44% and CYPC29 49% of the VKA dose variation.
Until the age of 19, weight has a far greater effect on VKA dosing variation than VKORC1 and CYP2C9 polymorphisms. During the age of 20-40years, VKORC1 and CYP2C9 play a significant role.
鉴于 VKORC1 和 CYP2C9 多态性在成人和儿童维生素 K 拮抗剂 (VKA) 剂量变化中的作用存在定性差异，我们有兴趣确定这些多态性从何时开始发挥更重要的作用。
一项前瞻性队列研究纳入了 190 名年龄在 1-86 岁的接受 VKA 治疗静脉血栓栓塞症的患者。在患者处于稳定的目标 INR（2-3）时采集血液样本，用于血浆检测和 VKORC1/CYP2C9 基因分型，此时患者已经度过急性血栓事件。收集患者的人口统计学资料，包括 VKA 剂量。采用简单和多元线性回归分析评估 VKA 剂量与多态性和体重的关系，调整抗凝质量（INR、D-二聚体）、肝（AST、ALT）和肾功能。
在 1-19 岁的患者中，体重解释了 39.0%的 VKA 剂量变化，而 VKORC1 和 CYP2C9 则起次要作用。相比之下，在 20-40 岁的患者中，体重、VKORC1 和 CYP2C9 分别贡献了 23%、44%和 49%的 VKA 剂量变化。
在 19 岁之前，体重对 VKA 剂量变化的影响远大于 VKORC1 和 CYP2C9 多态性。在 20-40 岁期间，VKORC1 和 CYP2C9 起重要作用。
