Influence of CYP4F2 rs2108622 (V433M) on Warfarin Dose Requirement in Asian Patients
Influence of CYP4F2 rs2108622 (V433M) on Warfarin Dose Requirement in Asian Patients
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DOI：
10.2133/dmpk.dmpk-10-rg-080
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发表时间：
2011-01-01
影响因子：
2.1
通讯作者：
Chowbay, Balram
中科院分区：
文献类型：
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作者：
Singh, Onkar;Sandanaraj, Edwin;Chowbay, Balram
Warfarin在给药要求方面表现出广泛的患者间差异。最近的研究表明，CYP 4F 2基因中的一种新的多态性（rs 2108622，V433 M）与高加索人华法林需求的变异性相关。本研究的目的是评价rs 2108622对亚洲人群华法林剂量需求的影响。发现携带纯合野生型等位基因CC的患者的平均华法林剂量显著低于携带变异等位基因CT和TT的患者（CC vs CT+TT：3.0 mg/d vs 3.75 mg/d，p = 0.033）。在携带VKORC 1双体型且华法林需求量低的患者中，包括年龄、体重、CYP 2C 9和CYP 4F 2变异体的线性回归模型解释了华法林剂量变异性的38%。约11%的剂量变化可由CYP 4F 2 rs 2108622解释（p = 0.004）。rs 2108622对携带与华法林高需求相关的VKORC 1双体型患者的影响不显著。这项研究表明，CYP 4F 2 rs 2108622可能会显着影响VKORC 1低剂量相关二倍体携带者的华法林剂量需求。
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.