Exploring warfarin pharmacogenomics with the extreme-discordant-phenotype methodology: impact of FVII polymorphisms on stable anticoagulation with warfarin
作者： Mateus Fuchshuber-Moraes , Jamila A Perini , Dieter Rosskopf , Guilherme Suarez-Kurtz , None
DOI: 10.1007/S00228-009-0651-6
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摘要: To explore the pharmacogenomics of warfarin using extreme-discordant-phenotype (EDP) methodology. The target phenotype was stable dose prescribed to 353 patients. Pharmacogenetic polymorphisms assessed were coagulation factor VII (FVII) -401G>T and FVII -402G>A, VKORC1 3673G>A, CYP2C9*2, *3, *5, *11 alleles. EDP analyses contrasted frequencies these at different cutoff points (5th through 30th percentiles distribution) opposite ends distribution. Significant differences existed in -402G>A genotype frequency 5th percentile with an over-representation wildtype GG low doses 3673G>A CYP2C9 all where variant alleles overrepresented doses. methodology provides increased statistical power for detection small contributions genetic multiplex drug-response phenotypes, such as requirement adequate anticoagulation.
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