Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, TN, USA.
Br J Haematol. 2014 Jun;165(6):832-5. doi: 10.1111/bjh.12817. Epub 2014 Mar 6.
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.
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%。
