Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients


Autoria(s): PERINI, J. A.; STRUCHINER, C. J.; SILVA-ASSUNCAO, E.; SANTANA, I. S. C.; RANGEL, F.; OJOPI, E. B.; DIAS-NETO, E.; SUAREZ-KURTZ, G.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2008

Resumo

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm`s predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm`s predictive power was similar across the self-identified ""race/color"" subsets. ""Race/color"" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

Swiss Bridge Foundation

Swiss Bridge Foundation

Financiadora de Estudos e Projetos (FINEP)

Financiadora de Estudos e Projetos (FINEP)

Associacao Beneficente Alzira Denise Hertzog Silva to the Laboratorio de Neurociencias

Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS)

Universidade de São Paulo - FM-USP

Universidade de São Paulo - FM-USP

Identificador

CLINICAL PHARMACOLOGY & THERAPEUTICS, v.84, n.6, p.722-728, 2008

0009-9236

http://producao.usp.br/handle/BDPI/31543

10.1038/clpt.2008.166

http://dx.doi.org/10.1038/clpt.2008.166

Idioma(s)

eng

Publicador

NATURE PUBLISHING GROUP

Relação

Clinical Pharmacology & Therapeutics

Direitos

restrictedAccess

Copyright NATURE PUBLISHING GROUP

Palavras-Chave #K EPOXIDE REDUCTASE #DOSE REQUIREMENTS #POPULATION ADMIXTURE #AFRICAN-AMERICANS #CYP2C9 GENOTYPES #HEMORRHAGIC COMPLICATIONS #COAGULATION-FACTOR #COMPLEX SUBUNIT-1 #VKORC1 #POLYMORPHISMS #Pharmacology & Pharmacy
Tipo

article

original article

publishedVersion