Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.
Clin Pharmacol Ther
; 92(6): 746-56, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23132553
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Cumarínicos
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Sistema Enzimático do Citocromo P-450
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Aged
/
Aged80
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Humans
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália