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Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis

Danese, E.; Montagnana, M.; Johnson, J. A.; Rettie, A. E.; Zambon, C. F.; Lubitz, S. A.; Suarez-Kurtz, G.; Cavallari, L. H.; Zhao, L. and Huang, M., et al. (2012) In Clinical Pharmacology and Therapeutics 92(6). p.746-756
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.... (More)
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. (Less)
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Clinical Pharmacology and Therapeutics
volume
92
issue
6
pages
746 - 756
publisher
Nature Publishing Group
external identifiers
  • wos:000311283400016
  • scopus:84869497712
ISSN
1532-6535
DOI
10.1038/clpt.2012.184
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English
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d5cffcd1-cdda-469a-bf65-c5342ab69a61 (old id 3379377)
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2013-02-01 07:02:22
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@article{d5cffcd1-cdda-469a-bf65-c5342ab69a61,
  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 &lt; 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.},
  author       = {Danese, E. and Montagnana, M. and Johnson, J. A. and Rettie, A. E. and Zambon, C. F. and Lubitz, S. A. and Suarez-Kurtz, G. and Cavallari, L. H. and Zhao, L. and Huang, M. and Nakamura, Y. and Mushiroda, T. and Kringen, M. K. and Borgiani, P. and Ciccacci, C. and Au, N. T. and Langaee, T. and Siguret, V. and Loriot, M. A. and Sagreiya, H. and Altman, R. B. and Shahin, M. H. A. and Scott, S. A. and Khalifa, S. I. and Chowbay, B. and Suriapranata, I. M. and Teichert, M. and Stricker, B. H. and Taljaard, M. and Botton, M. R. and Zhang, J. E. and Pirmohamed, M. and Zhang, X. and Carlquist, J. F. and Horne, B. D. and Lee, M. T. M. and Pengo, V. and Guidi, G. C. and Minuz, P. and Fava, Cristiano},
  issn         = {1532-6535},
  language     = {eng},
  number       = {6},
  pages        = {746--756},
  publisher    = {Nature Publishing Group},
  series       = {Clinical Pharmacology and Therapeutics},
  title        = {Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis},
  url          = {http://dx.doi.org/10.1038/clpt.2012.184},
  volume       = {92},
  year         = {2012},
}