In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes
In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes
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DOI：
10.1182/blood-2010-05-283861
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发表时间：
2010-12-23
期刊：
影响因子：
20.3
通讯作者：
Mitchell, Lesley G.
中科院分区：
文献类型：
--
作者：
Nowak-Goettl, Ulrike;Dietrich, Kevin;Mitchell, Lesley G.
维生素K拮抗剂(VKA)的抗凝是有问题的，因为安全地管理剂量是困难的。细胞色素P450 2C9(细胞色素P450 2C9)和维生素K环氧化物还原酶基因(VKORC1)的多态已被证明影响成人VKA的剂量。这些基因多态与儿童VKA剂量之间的关系尚未得到研究。这项研究的目的是评估CYP2C9和VKORC1基因多态性与儿童VKA剂量的临床变量之间的关系。对接受VKA治疗的未选择的儿科患者进行了CYP2C9和VKORC1基因的多态性检测，并收集了临床数据。使用多元线性回归模型评估VKA剂量与遗传变量和临床变量的关系。59名患者被招募；55.9%的患者接受华法林治疗，441%的患者接受苯普鲁蒙治疗。年龄与VKA剂量呈负相关(P<；.001)。比较VKORC1型，AA组每日所需剂量显著低于GG组(P=.011)。在包括年龄在内的全模型中，VKORC1和CYP2C9两种基因型别可解释38%的剂量变异。年龄可以解释28.3%的VKA剂量变异，VKORC1和CYP2C9分别只解释3.7%和0.4%。在儿童中，决定VKA剂量的最关键因素是年龄。VKORC1/CYP2C9基因只能略微解释剂量变化。(血。2010；116(26)：6101-6105)
Anticoagulation with vitamin K antagonists (VKAs) is problematic because of difficulties in safely managing dosing. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase genes (VKORC1) have been shown to affect VKA dosing in adults. The association of these polymorphisms on VKA dosing in children has not been investigated. The objective of the study was to assess associations of CYP2C9 and VKORC1 polymorphisms and clinical variables on VKA dosing in children. Anonselected cohort of pediatric patients receiving VKA were tested for CYP2C9 and VKORC1 polymorphisms, and clinical data were collected. Multiple linear regression modeling was used to assess relationships of VKA dose with genetic and clinical variables. Fifty-nine patients were recruited; 55.9% were receiving warfarin, and 44.1% were on phenprocoumon. There was a negative association of age with VKA dose (P < .001). Comparing VKORC1 genotypes, the AA group required significantly lower daily doses than GG group (P = .011). In the full model including age, VKORC1 and CYP2C9 genotypes accounted for 38% of dose variation. Age explained 28.3% of VKA dose variations; VKORC1 and CYP2C9 explained only 3.7% and 0.4%, respectively. In children, the most critical factor in determining VKA dose is age. VKORC1/CYP2C9 genotypes only marginally explain dose variations. (Blood. 2010; 116(26):6101-6105)