Influence of CYP4F2 genotype on warfarin dose requirement-a systematic review and meta-analysis

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• 作者：Ruijuan Liang ; Chunling Wang ; Hong Zhao ; Jie Huang ; Dayi Hu ; Yihong Sun ; ^{yihongsun72@163.com}
• 关键词：INR ; International Normalized Ratio ; CYP2C9 ; CytochromeP450 Complex Subunit2C9 ; VKORC1 ; Vitamin K Epoxide Reductase Complex Subunit 1 ; CYP4F2 ; CytochromeP450 Complex Subunit 14  ; F2 ; CI ; Confidence Interval ; HLM ; Human Liver Microsomes ; MDWD ; Mean Dail
• 刊名：Thrombosis Research
• 出版年：2012
• 期刊代码：247_00493848
• 类别：med
• 出版时间：July, 2012
• 卷：130
• 期：1
• 页码：38-44
• 文件大小：1382 K

摘要

Introduction

Warfarin is a commonly used oral anticoagulant and the dosage is individually adjusted on the basis of the international normalized ratio (INR) monitoring. It is well known that gene polymorphisms of CytochromeP450 (CYP) 2 C9 gene and the vitamin K epoxide reductase complex 1 (VKORC1) were significantly associated with warfarin dose. However, the association between Cytochrome P450 4 F2 (CYP4F2) polymorphism and warfarin dose requirement is still controversial. This study was to investigate the influence of the CYP4F2 polymorphism, V433M (rs2108622) on warfarin dose for patients by meta-analysis.

Methods

Strict inclusion and exclusion criteria were set, and the studies prior to December 19, 2010 were searched in PubMed, EMBASE and CNKI. References were examined and experts of primary studies were consulted for additional information. Revman 5.0.2 software was used to analyze the relationship between warfarin maintenance dose and CYP4F2 polymorphism

Results

Thirteen studies were included in the meta-analysis which consisted of Caucasian, Asian and African populations. Compared to individuals with the homozygous CYP4F2 genotype (CC), carriers of CT, TT genotypes required 10.0%(95%confidence interval(CI) 4.0-15.0) and 21.0%(95%CI 9.0-33.0) higher warfarin doses respectively (P value < 0.05). In addition, T carriers required 11.0%(95%CI 6.0-17.0) higher warfarin dose than CC genotype.

Conclusions

Our study showed that polymorphism of CYP4F2 had a moderate but statistically significant association with the variation of interindividual warfarin dose. However, whether CYP4F2 can improve the prediction of warfarin dose warrants need further investigation when combined with environmental factors.