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BIBTEX RIS

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

2012; Wiley; Volume: 92; Issue: 6 Linguagem: Inglês

10.1038/clpt.2012.184

ISSN

1532-6535

Autores

Elisa Danese, Martina Montagnana, Julie A. Johnson, Allan E. Rettie, Carlo–Federico Zambon, Steven A. Lubitz, Guilherme Suarez‐Kurtz, Larisa H. Cavallari, Lidong Zhao, Min Huang, Yusuke Nakamura, Taisei Mushiroda, Marianne Kristiansen Kringen, Paola Borgiani, Cinzia Ciccacci, Nicholas T. Au, Taimour Langaee, Virginie Siguret, Marie‐Anne Loriot, Hersh Sagreiya, Russ B. Altman, Mohamed H. Shahin, Stuart A. Scott, Sherief Khalifa, Balram Chowbay, Ivet Suriapranata, Martina Teichert, Bruno H. Stricker, Monica Taljaard, Mariana Rodrigues Botton, J. E. Zhang, Munir Pirmohamed, X Zhang, John F. Carlquist, Benjamin D. Horne, M T M Lee, Vittorio Pengo, Gian Cesare Guidi, Pietro Minuz, Cristiano Fava,

Tópico(s)

Health Systems, Economic Evaluations, Quality of Life

Resumo

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 (I2 = 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. Clinical Pharmacology & Therapeutics (2012); 92 6, 746–756. doi:10.1038/clpt.2012.184

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