Clinical Pharmacology Laboratory, Humphrey Oei Institute of Cancer Research, National Cancer Center, Singapore.
Drug Metab Pharmacokinet. 2011;26(2):130-6. doi: 10.2133/dmpk.dmpk-10-rg-080. Epub 2010 Nov 12.
Warfarin exhibits wide interpatient variability in dosing requirements. Recent studies have shown a novel polymorphism (rs2108622, V433M) in the CYP4F2 gene to be associated with variability in warfarin requirements in Caucasians. The purpose of this study was to evaluate the impact of rs2108622 on warfarin dose requirements in the Asian population. The mean warfarin dose was found to be significantly lower in patients carrying homozygous wild-type allele CC when compared with patients carrying variant alleles CT and TT (CC vs CT+TT: 3.0 mg/day vs 3.75 mg/day, p = 0.033). In patients harboring VKORC1 diplotypes associated with low warfarin requirements, a linear regression model which included age, weight, CYP2C9 and CYP4F2 variants accounted for 38% of the variability in warfarin dose. Approximately 11% of the dose variation was explained by CYP4F2 rs2108622 (p = 0.004). The influence of rs2108622 in patients harboring VKORC1 diplotypes associated with high warfarin requirements was not significant. This study suggests that CYP4F2 rs2108622 may significantly affect warfarin dose requirements in carriers of VKORC1 low-dose-associated diplotypes.
华法林在剂量需求方面表现出广泛的个体间变异性。最近的研究表明，CYP4F2 基因中的一种新的多态性（rs2108622，V433M）与高加索人群中华法林需求的变异性相关。本研究旨在评估 rs2108622 对亚洲人群华法林剂量需求的影响。与携带变异等位基因 CT 和 TT 的患者相比，携带纯合野生型等位基因 CC 的患者的平均华法林剂量明显较低（CC 与 CT+TT：3.0mg/天与 3.75mg/天，p=0.033）。在携带与低华法林需求相关的 VKORC1 二倍型的患者中，包含年龄、体重、CYP2C9 和 CYP4F2 变异体的线性回归模型解释了华法林剂量变化的 38%。CYP4F2 rs2108622 解释了约 11%的剂量变化（p=0.004）。在携带与高华法林需求相关的 VKORC1 二倍型的患者中，rs2108622 的影响并不显著。本研究表明，CYP4F2 rs2108622 可能显著影响携带 VKORC1 低剂量相关二倍型的患者的华法林剂量需求。
