Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.

Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.

Clinical pharmacology and therapeutics (2012-11-08)

E Danese, M Montagnana, J A Johnson, A E Rettie, C F Zambon, S A Lubitz, G Suarez-Kurtz, L H Cavallari, L Zhao, M Huang, Y Nakamura, T Mushiroda, M K Kringen, P Borgiani, C Ciccacci, N T Au, T Langaee, V Siguret, M A Loriot, H Sagreiya, R B Altman, M H A Shahin, S A Scott, S I Khalifa, B Chowbay, I M Suriapranata, M Teichert, B H Stricker, M Taljaard, M R Botton, J E Zhang, M Pirmohamed, X Zhang, J F Carlquist, B D Horne, M T M Lee, V Pengo, G C Guidi, P Minuz, C Fava

PMID23132553

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.

MATERIALS

Product Number

Brand

Product Description

01260595

Coumarin, primary reference standard

72609

Supelco

Coumarin, certified reference material, TraceCERT^®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland

C4261

Sigma-Aldrich

Coumarin, ≥99% (HPLC)

Y0000438

Coumarin, European Pharmacopoeia (EP) Reference Standard