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. 2011 Sep;72(3):442-50.
doi: 10.1111/j.1365-2125.2011.03942.x.

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

Mariana Rodrigues Botton  1 , Eliane Bandinelli, Luis Eduardo Paim Rohde, Luis Carlos Amon, Mara Helena Hutz
Affiliations

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

Mariana Rodrigues Botton et al. Br J Clin Pharmacol. 2011 Sep.

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.

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Figures

Figure 1
Figure 1
Relationship between the predicted dose by our algorithm and the observed dose in patients
See this image and copyright information in PMC

Comment in

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