Clinical Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, P.O. Box 99, Manial El-Roda, Cairo, 11553, Egypt.
Paediatr Drugs. 2014 Aug;16(4):337-41. doi: 10.1007/s40272-014-0073-5.
Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent.
CYP2C9 (*2 and *3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose.
The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 -1639A (0.54). In univariate analysis, patients' age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045).
Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.
华法林是一种广泛使用的抗凝剂，其在达到目标抗凝效果所需的剂量方面存在高度个体间差异。在成年人中，细胞色素 P450-2C9（CYP2C9）和维生素 K 环氧化物还原酶复合物（VKORC1）酶中的常见遗传变异，以及非遗传因素，解释了这种剂量变异性。在儿童中，关于华法林药物遗传学的数据有限且不一致。
通过多重实时聚合酶链反应，在接受稳定华法林维持剂量的 41 名儿科患者中研究了 CYP2C9（*2 和 *3）等位基因和 VKORC1（C1173T 和 G-1639A）多态性。
研究基因的等位基因频率为 CYP2C92（0.085）、CYP2C93（0.12）、VKORC1 1173T（0.52）和 VKORC1-1639A（0.54）。在单变量分析中，患者的年龄、体重和身高与华法林维持剂量显著相关（p < 0.0001）。然而，CYP2C9 和 VKORC1 基因多态性并不影响华法林剂量。在多变量分析中，发现年龄是每日华法林维持剂量的唯一显著决定因素（p = 0.045）。
在这项包括埃及儿科患者的初步研究中，年龄是华法林剂量的最重要决定因素。需要进一步进行涉及更多儿童的研究，以确定遗传因素对华法林剂量在儿科患者中的真实影响。
