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Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2012 Dec; Vol. 92 (6), pp. 746-56. Date of Electronic Publication: 2012 Nov 07. - Publication Year :
- 2012
-
Abstract
- A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
- Subjects :
- Aged
Aged, 80 and over
Algorithms
Alleles
Aryl Hydrocarbon Hydroxylases genetics
Cohort Studies
Coumarins therapeutic use
Cross-Sectional Studies
Cytochrome P-450 CYP2C9
Cytochrome P450 Family 4
Ethnicity
Humans
International Normalized Ratio
Middle Aged
Mixed Function Oxygenases genetics
Publication Bias
Sex Factors
Vitamin K Epoxide Reductases
Coumarins administration & dosage
Cytochrome P-450 Enzyme System genetics
Polymorphism, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-6535
- Volume :
- 92
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 23132553
- Full Text :
- https://doi.org/10.1038/clpt.2012.184