Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients.
Thromb Res
; 120(2): 181-6, 2007.
Article
em En
| MEDLINE
| ID: mdl-17049586
ABSTRACT
The dose required for the anticoagulant effect of warfarin exhibits large inter-individual variations. This study sought to determine the contribution of four genes, vitamin K epoxide reductase (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU), and cytochrome P450 2C9 (CYP2C9) to the warfarin maintenance dose required in Japanese patients following ischemic stroke. We recruited 93 patients on stable anticoagulation with a target International Normalized Ratio (INR) of 1.6-2.6. We genotyped eleven representative single nucleotide polymorphisms (SNPs) in the three genes involved in vitamin K cycle and the 42613A>C SNP in CYP2C9, known as CYP2C93, and then examined an association of these genotypes with warfarin maintenance doses (mean+/-SD=2.96+/-1.06 mg/day). We found an association of effective warfarin dose with the -1639G>A (p=0.004) and 3730G>A genotypes (p=0.006) in VKORC1, the 8016G>A genotype in GGCX (p=0.022), and the 42613A>C genotype in CYP2C9 (p=0.015). The model using the multiple regression analysis including age, sex, weight, and three genetic polymorphisms accounted for 33.3% of total variations in warfarin dose. The contribution to inter-individual variation in warfarin dose was 5.9% for VKORC1 -1639G>A, 5.2% for CYP2C9 42613A>C, and 4.6% for GGCX 8016G>A. In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients.
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Base de dados:
MEDLINE
Assunto principal:
Varfarina
/
Hidrocarboneto de Aril Hidroxilases
/
Carbono-Carbono Ligases
/
Oxigenases de Função Mista
/
Anticoagulantes
Tipo de estudo:
Diagnostic_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article