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Meta-Analysis
. 2012 Dec;92(6):746-56.
doi: 10.1038/clpt.2012.184. Epub 2012 Nov 7.

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

E Danese  1 , 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
Affiliations
Meta-Analysis

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

E Danese et al. Clin Pharmacol Ther. 2012 Dec.

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.

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Conflict of interest statement

CONFLICT OF INTEREST

J.A.J. is a member of the Clarification of Optimal Anticoagulation Through Genetics (COAG) clinical trial executive committee. S.A.S.,T.L, and J.F.C. are members of the COAG genotyping committee. The other authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram showing the number of citations identified, retrieved, extracted, and included in the final analysis.
Figure 2
Figure 2
Effect of the CYP4F2 rs2108622 C>T polymorphism on coumarin dosage requirement per the dominant genetic model (CC vs. CT&TT). CI, confidence interval.
Figure 3
Figure 3
Effect of the CYP4F2 rs2108622 C>T polymorphism on coumarin dose requirements in subgroups categorized by gender. CI, confidence interval.
Figure 4
Figure 4
Effect of the CYP4F2 rs2108622 C>T polymorphism on coumarin dose requirements in different ethnic subgroups. CI, confidence interval.
Figure 5
Figure 5
Funnel plot for association studies of the CYP4F2 rs2108622 OT polymorphism on coumarin dose requirements. The solid vertical line represents the summary effect estimate, derived by using fixed-effects metaanalysis, for displaying the center of the plot in the absence of bias. The diagonal lines represent 95% confidence limits for the expected distribution of studies in the absence of heterogeneity between studies and absence of selection biases.
See this image and copyright information in PMC

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