年龄及 CYP2C9 和 VKORC1 变异体对儿科人群稳定华法林剂量的影响。
The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population.
机构信息
Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, TN, USA.
出版信息
Br J Haematol. 2014 Jun;165(6):832-5. doi: 10.1111/bjh.12817. Epub 2014 Mar 6.
Abstract
The influence of genetic variation on warfarin dose requirement is limited for paediatric patients. We performed a retrospective, cross-sectional study to examine the effect of variant CYP2C9 and VKORC1 genotypes on warfarin dose in 100 children. Those with VKORC1 genotype AA required 48% of the dose of homozygous wild-type (GG, P < 0·0001). Patients with any variant CYP2C9 allele required 71% of the dose for wild-type (P = 0·001). The effect of variant VKORC1 alleles tended to vary with age, suggesting developmental ontogeny may influence warfarin sensitivity. Age, CYP2C9 genotype, VKORC1 genotype and age:VKORC1 interaction accounted for 53% of warfarin dose variability.
摘要
遗传变异对儿童华法林剂量需求的影响有限。我们进行了一项回顾性、横断面研究，以研究 100 例儿童中变异 CYP2C9 和 VKORC1 基因型对华法林剂量的影响。VKORC1 基因型为 AA 的患者所需剂量为纯合野生型（GG）的 48%（P<0.0001）。任何变异 CYP2C9 等位基因的患者所需剂量为野生型的 71%（P=0.001）。变异 VKORC1 等位基因的作用似乎随年龄而变化，提示发育发生可能影响华法林敏感性。年龄、CYP2C9 基因型、VKORC1 基因型和年龄：VKORC1 相互作用占华法林剂量变异性的 53%。
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