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Effect of gene polymorphims on the warfarin treatment at initial stage

The Pharmacogenomics Journal volume 17, pages 47–52 (2017)Cite this article

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Abstract

The adverse reactions of warfarin that were found mainly occurred in the first month. This study was carried out to observe the effect of gene polymorphisms on the warfarin therapy at the initial stage. Four-hundred and sixty Chinese patients began warfarin treatment with daily 2.5 mg after heart valve replacement operations were enrolled. The daily international normalized ratio (INR) for anticoagulation were recorded till the seventh day. Blood samples were collected and used to detect genotypes for VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650. INR and their changes were compared among genotypes. INR was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 polymorphisms from the third, fourth and sixth day on, respectively. VKORC1 rs7294 and CYP4F2 rs2108622 carriers responded lower than the wild genotype, whereas CYP2C9 rs1057910 and ORM1 rs17650 carriers responded higher, respectively. Fifty percent of AA/*1*3/CC/*S*S patients and 16% of AA/*1*1/CC/*S*S patients were over anticoagulation treated with INR >4.0 at the third day. Ninety percent of VKORC1 rs7294 carrier patients have INR <1.63, a mark of the 25% of lower responders of the wild genotype. Our study provided another kind of evidence that VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 affected the action of warfarin in different styles. Patients with AA/*1*1/CC/*S*S, AA/*1*3/CC/*S*S should use a less initial dosage to avoid over anticoagulation, and patients with VKORC1 rs7294 should use larger initial dose to proof an effective therapy.

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Acknowledgements

All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: this study was funded by the National Scientific Foundation of China (No. 81072707, 81472031, 81273595 and 81101331), 863 Project (No. 2012AA02A518). No other relationships or activities exist that could have influenced the submitted work.

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Author notes

  1. J Liu and H H Jiang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China

    J Liu, Y X Zhou, X Li, Z Y Luo, Z Guo, Y L Zhang, Y C Wang, W Zhang, H H Zhou & L S Wang

  2. Institute of Clinical Pharmacology, Central South University, Changsha, China

    J Liu, Y X Zhou, X Li, Z Y Luo, Z Guo, Y L Zhang, Y C Wang, W Zhang, H H Zhou & L S Wang

  3. Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, China

    H H Jiang & D K Wu

  4. Department of Clinical Laboratory, Zhongshan Hospital Xiamen University Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China

    H M Ye

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Correspondence to L S Wang.

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Author contributions

JL helped to collect and analyze the data, and to write the manuscript. HHJ, DKW and HMY helped to coordinate the study. YXZ helped to collect the samples. XL helped to analyze the data. ZYL and ZG helped to collect the data. YLZ helped to perform the statistical analysis. YCW, WZ and HHZ helped to coordinate the study. LSW has designed and organized the study, has analyzed and interpreted the data, and writen the manuscript and confirmed the final approval of the version.

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Liu, J., Jiang, H., Wu, D. et al. Effect of gene polymorphims on the warfarin treatment at initial stage. Pharmacogenomics J 17, 47–52 (2017). https://doi.org/10.1038/tpj.2015.81

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