Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.
Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.
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DOI：
10.1038/clpt.2012.184
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发表时间：
2012-12
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
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采用系统综述和荟萃分析的方法，量化从研究CYP4F2 rs2108622(p.V433M)多态对香豆素剂量需求影响的遗传关联研究中积累的信息。另一个目的是通过与VKORC1和CYP2C9变异体的比较以及分层后，探索CYP4F2变异体的贡献。涉及9,470名参与者的30项研究符合预先指定的纳入标准。与CC纯合子相比，T等位基因携带者需要比CC纯合子每天平均香豆素剂量高8.3%(95%可信区间：5.6-11.1%；P<；0.0001)才能达到稳定的国际标准化比。没有证据表明存在发表偏见。研究之间存在异质性(I2=43%)。我们的结果表明，CYP4F2p.V433M多态与香豆素类药物的个体间变异性有关，但其效应大小较VKORC1和CYP2C9多态所致。
A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6–11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
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