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Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry.


ABSTRACT: AIMS:To investigate the influence of polymorphisms in CYP2C9, VKORC1, CYP4F2 and F2 genes on warfarin dose-response and develop a model including genetic and non-genetic factors for warfarin dose prediction needed for each patient. METHODS:A total of 279 patients of European ancestry on warfarin medication were investigated. Genotypes for -1639G>A, 1173C>T, and 3730G>A SNPs in the VKORC1 gene, CYP2C9*2 and CYP2C9*3, 1347C>T in the CYP4F2 gene and 494C>T in the F2 gene were determined by allelic discrimination with Taqman 5'-nuclease assays. RESULTS:The CYP2C9*2 and CYP2C9*3 polymorphisms in the CYP2C9 gene, -1639G>A and 1173C>T in the VKORC1 gene and 494C>T in the F2 gene are responsible for lower anticoagulant doses. In contrast, 1347C>T in the CYP4F2 gene and 3730G>A in the VKORC1 gene are responsible for higher doses of warfarin. An algorithm including genetic, biological and pharmacological factors that explains 63.3% of warfarin dose variation was developed. CONCLUSION:The model suggested has one of the highest coefficients of determination among those described in the literature.

SUBMITTER: Botton MR 

PROVIDER: S-EPMC3175513 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry.

Botton Mariana Rodrigues MR   Bandinelli Eliane E   Rohde Luis Eduardo Paim LE   Amon Luis Carlos LC   Hutz Mara Helena MH  

British journal of clinical pharmacology 20110901 3


<h4>Aims</h4>To investigate the influence of polymorphisms in CYP2C9, VKORC1, CYP4F2 and F2 genes on warfarin dose-response and develop a model including genetic and non-genetic factors for warfarin dose prediction needed for each patient.<h4>Methods</h4>A total of 279 patients of European ancestry on warfarin medication were investigated. Genotypes for -1639G>A, 1173C>T, and 3730G>A SNPs in the VKORC1 gene, CYP2C9*2 and CYP2C9*3, 1347C>T in the CYP4F2 gene and 494C>T in the F2 gene were determi  ...[more]

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