Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350001, PR China.
Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, PR China.
Thromb Res. 2015 Nov;136(5):955-61. doi: 10.1016/j.thromres.2015.09.018. Epub 2015 Sep 26.
Warfarin is the most commonly used oral anticoagulant, however, there are large interindividual variations in dose responses. Genetic polymorphisms in CYP2C9, VKORC1 and CYP4F2 have been shown to play an important role in variations in the warfarin maintenance dose in adults, but their effects in children remain unclear. We aimed to investigate the effect of VKORC1 polymorphism on warfarin dosage in pediatric patients by meta-analysis.
Using strict inclusion and exclusion criteria, we searched PubMed, EMBASE, Cochrane library, Chinese Biomedical Literature Database, CNKI and ChainInfo from 2004 to Mach 17th, 2015. The relationship between warfarin dose and two single nucleotide polymorphisms of the VKORC1 gene (at positions -1639 and 1173) were analyzed using Revman version 5.2.3 software.
Eight studies were included in the meta-analysis, involving 610 pediatric patients. Patients that were VKORC1 -1639 GA, AA or A carriers required significantly lower warfarin dosage than GG carriers (the weighted mean difference in warfarin dose ranged from -26% to -50%). Additionally, the age of the patient and indication of warfarin (i.e. Fontan procedure) significantly affected warfarin dosage, but changes in the target international normalized ratio range had no effect. On the other hand, VKORC1 1173 polymorphisms showed no significant effect on warfarin dosage, which differs from adult patients. In conclusion, we found that VKORC1 -1639 gene polymorphisms have a moderate effect on warfarin dosage in pediatric patients, but clinical characteristics such as age and indication of warfarin also play an important role.
华法林是最常用的口服抗凝剂，但剂量反应存在很大的个体差异。CYP2C9、VKORC1 和 CYP4F2 的基因多态性已被证明在成人华法林维持剂量的变化中起着重要作用，但它们在儿童中的作用仍不清楚。我们旨在通过荟萃分析研究 VKORC1 多态性对华法林剂量在儿科患者中的影响。
使用严格的纳入和排除标准，我们检索了 2004 年至 2015 年 3 月 17 日的 PubMed、EMBASE、Cochrane 图书馆、中国生物医学文献数据库、CNKI 和 ChainInfo。使用 Revman 版本 5.2.3 软件分析华法林剂量与 VKORC1 基因（位于-1639 位和 1173 位）的两个单核苷酸多态性之间的关系。
共纳入 8 项研究，涉及 610 例儿科患者。VKORC1-1639GA、AA 或 A 携带者所需的华法林剂量明显低于 GG 携带者（华法林剂量的加权均数差范围为-26%至-50%）。此外，患者的年龄和华法林的适应证（即 Fontan 手术）显著影响华法林的剂量，但目标国际标准化比值范围的变化没有影响。另一方面，VKORC1 1173 多态性对华法林剂量没有显著影响，这与成年患者不同。总之，我们发现 VKORC1-1639 基因多态性对华法林在儿科患者中的剂量有中等影响，但年龄和华法林适应证等临床特征也起着重要作用。
