European Journal of Clinical Pharmacology

, Volume 65, Issue 4, pp 365–375

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

Authors

    • Division of Clinical PharmacologyKarolinska Institutet
    • Department of Clinical Pharmacology, C1–68Karolinska University Hospital Huddinge
  • Lennart Holm
    • Division of Clinical PharmacologyKarolinska Institutet
  • Marine L. Andersson
    • Division of Clinical PharmacologyKarolinska Institutet
  • Anders Rane
    • Division of Clinical PharmacologyKarolinska Institutet
Pharmacogenetics

DOI: 10.1007/s00228-008-0584-5

Cite this article as:
Lindh, J.D., Holm, L., Andersson, M.L. et al. Eur J Clin Pharmacol (2009) 65: 365. doi:10.1007/s00228-008-0584-5

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.

Keywords

WarfarinCYP2C9PharmacogeneticsGenetic polymorphismMeta-analysisDrug interactions

Copyright information

© Springer-Verlag 2008