Pharmacogenetic impact of VKORC1 and CYP2C9 allelic variants on warfarin dose requirements in a hispanic population isolate.
Clin Appl Thromb Hemost
; 16(1): 83-90, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-19567378
Warfarin is the most prescribed oral anticoagulant worldwide. Because of the complexity of warfarin therapy, we attempted to dissect genetic from bioenvironmental factors influencing warfarin dose responses in individuals of a genetic isolate of Hispanic ancestry. A total of 191 patients with standard values of international normalized ratio were recruited. Three groups with a significantly different warfarin dose response were identified, that is, sensitive (2.28 +/- 0.50 mg/d), intermediate (4.2 +/- 0.76 mg/d), and resistant (7.40 +/- 1.54 mg/d; Tukey test, P < .001). Age had a significant inverse correlation with warfarin dose (P < .001; effective dose diminished 0.56 mg/d/decade). Required doses were higher for individuals with CYP2C9 variants containing the allele *1 compared to those individuals with variants composed of other alleles (P = .006). Similarly, individuals with VKORC1-1639GG and VKORC1-1639GA genotypes also required higher doses compared to the AA genotype (P < .001). Evaluation of potential gene-gene interactions between CYP2C9 and VKORC1 polymorphisms showed significant differences in dosing for CYP2C9 genotypes within the VKORC1-1639G/A subgroup (P = .013). A stepwise multivariate linear regression analysis showed that 38.2% of the warfarin dose response variance was accounted for by a model involving age (20.9%), VKORC1-1639G/A (11.3%), and CYP2C9*1, *2, and *3 variants (7.1%). These results corroborate previous findings on warfarin pharmacogenetics and define a contrastable gene-bioenvironment interaction model suited to be used in Hispanic populations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Varfarina
/
Hidrocarboneto de Aril Hidroxilases
/
Oxigenases de Função Mista
/
Anticoagulantes
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do sul
/
Colombia
Idioma:
En
Revista:
Clin Appl Thromb Hemost
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Colômbia
País de publicação:
Estados Unidos