CYP4F2rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement

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Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Genetic polymorphisms ofVKORC1andCYP2C9are known to influence warfarin dosage.• Recent studies among Caucasians showed that polymorphisms ofCYP4F2also play a role in warfarin pharmacogenetics.• The contribution ofCYP4F2variants to the variability inwarfarin dose requirement in Chinese subjects remains to be investigated.WHAT THIS STUDY ADDS• This research was to study the effect ofCYP4F2variants on warfarin requirements in the Han Chinese population.• This study developed a multiple regression model includingCYP2C9,VKORC13673G>A,CYP4F2genotypes and age, weight, combination use of amiodarone which could explain 56.1% of the individual variability in warfarin doseCYP4F2could explain 4% of the variance in warfarin dose.• We found that one novel genotypic polymorphism 5417G>T for Asp36Tyr, which was identified as an important marker of warfarin resistance, was absent in the Han Chinese population in our study.AIMS: The objective of this study was to assess the effect of theCYP4F2on the daily stable warfarin dose requirement in Han Chinese patients with mechanical heart valve replacement (MHVR).METHODS: From March 2007 to November 2008, 222 Han Chinese MHVR patients were recruited in our study.VKORC13673G>A, 5417G>T,CYP2C9*3 andCYP4F2rs2108622 were genotyped by using the polymerase chain reaction restriction fragment length polymorphism method (PCR‐RFLP). Polymorphisms ofVKORC19041G>A were detected by direct sequencing. Multiple linear regression analysis was used to investigate the contribution ofCYP4F2.RESULTS: TheCYP4F2rs2108622 CT/TT group took a significantly higher stable warfarin dose (3.2 mg day−1) than the CC group (2.9 mg day−1, 95% CI 0.2, 1.0,P= 0.033). The multiple linear regression model includedVKORC13673G>A,CYP2C9,CYP4F2genotypes and clinical characteristics. The model could explain 56.1% of the variance in stable warfarin dose in Han Chinese patients with MHVR.CYP4F2contributed about 4% to the variance in the warfarin dose. There was no variation in the SNPs ofVKORC15417G>T.CONCLUSION: CYP4F2is a minor significant factor of individual variability in the stable warfarin dose in Han Chinese patients with MHVR. The effect ofCYP2C9andVKORC1genotypes on variability in the stable warfarin dose had also been confirmed.

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