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

• Published in: European journal of clinical pharmacology 2009-04, Vol.65 (4), p.365-375
• Main Authors: Lindh, Jonatan D, Holm, Lennart, Andersson, Marine L, Rane, Anders
• Format: Article
• Language: English
• Subjects: Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - metabolism; Anticoagulants - pharmacokinetics; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood. Blood coagulation. Reticuloendothelial system; CYP2C9; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Drug dosages; Drug Interactions; Drug therapy; European Continental Ancestry Group - genetics; genetic polymorphism; Genotype; Genotype & phenotype; Humans; Linear Models; Medical sciences; Medicin och hälsovetenskap; Meta-analysis; Pharmacogenetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polymorphism; Polymorphism, Genetic; Prescription drugs; warfarin; Warfarin - administration & dosage; Warfarin - pharmacokinetics
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-008-0584-5

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.