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Pharmazie ; 79(7): 173-177, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39152554

RESUMO

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.


Assuntos
Anticoagulantes , Polimorfismo de Nucleotídeo Único , Varfarina , Humanos , Varfarina/administração & dosagem , Feminino , Masculino , Anticoagulantes/administração & dosagem , Idoso , Pessoa de Meia-Idade , Povo Asiático/genética , Japão , Coeficiente Internacional Normatizado , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular , Vitamina K Epóxido Redutases/genética , Idoso de 80 Anos ou mais , Família 4 do Citocromo P450/genética , Genótipo , Adulto , População do Leste Asiático
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