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Influence of CYP2C9 genotype on warfarin dose requirements—a systematic review and meta-analysis

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To quantify the influence of common cytochrome P450 2C9 (CYP2C9) polymorphisms on warfarin dose requirements.

Methods

A systematic review and a meta-analysis, calculating the warfarin dose reduction associated with the five most common variant CYP2C9 genotypes.

Results

Thirty-nine studies (7,907 patients) were included in the meta-analysis. Compared to the CYP2C9*1/*1 genotype, the CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3, and CYP2C9*3/*3 required warfarin doses that were 19.6 (95% confidence interval 17.4, 21.9), 33.7 (29.4, 38.1), 36.0 (29.9, 42.0), 56.7 (49.1, 64.3), and 78.1% (72.0, 84.3) lower, respectively. The impact of CYP2C9 genotype tended to be larger in patients without interacting drugs.

Conclusions

Previous studies have rarely been powered to determine the quantitative influence of specific CYP2C9 genotypes on warfarin dose requirements. The results from our pooled analysis are likely to be the most accurate to date and the methodology could serve as a model for future pharmacogenetic meta-analyses.

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Acknowledgements

J.D. Lindh is supported by the Swedish Foundation for Strategic Research. The project was partly supported by the Swedish Science Council (Medicine 04496), and the Swedish Drugs and Therapeutics Committee of Southwest Stockholm.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Jonatan D. Lindh, Lennart Holm, Marine L. Andersson & Anders Rane

  2. Department of Clinical Pharmacology, C1–68, Karolinska University Hospital Huddinge, S-14186, Stockholm, Sweden

    Jonatan D. Lindh

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  1. Jonatan D. Lindh
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  2. Lennart Holm
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Correspondence to Jonatan D. Lindh.

Appendix

Appendix

PubMed

Warfarin as MeSH or text word was combined with each of the following search phrases:

  • MeSH

  • Cytochromes

  • Cytochrome p-450 enzyme system

  • Genotype

  • Genes

  • Genetics

  • Alleles

  • Polymorphism, genetic

  • Pharmacogenetics

  • Text words

  • Cytochrome

  • Cytochromes

  • Cytochrome-p-450

  • Cytochrome p-450

  • p-450

  • Cytochrome P450

  • Cytochrome P 450

  • cyp2c9

  • 2c9

  • cyp2c

  • Genotype

  • Genotypes

  • Gene

  • Genes

  • Genetic

  • Genetics

  • Allele

  • Alleles

  • Polymorphism

  • Polymorph

  • Polymorphisms

  • Polymorphic

  • Pharmacogenetics

  • EMBASE

  • Warfarin/exp AND cytochrome p450 2c9/exp

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Lindh, J.D., Holm, L., Andersson, M.L. et al. Influence of CYP2C9 genotype on warfarin dose requirements—a systematic review and meta-analysis. Eur J Clin Pharmacol 65, 365–375 (2009). https://doi.org/10.1007/s00228-008-0584-5

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  • DOI: https://doi.org/10.1007/s00228-008-0584-5

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