INTRODUCTION: To establish individualized warfarin therapy, we investigated the contribution of genetic variations of vitamin K epoxide reductase complex subunit 1 gene (VKORC1) -1639 G>A and Cytochrome P450 2C9 gene (CYP2C9) and clinical factors on warfarin sensitivity in Japanese patients. MATERIALS AND METHODS: Genetic analyses of VKORC1 -1639 G>A and CYP2C9 2, 3, and 4 were performed in 259 Japanese patients and 341 healthy subjects. We selected 259 patients who have been prescribed warfarin with a 1.5-3.0 range of prothrombin time normalized as an international normalized ratio for at least 3 months and investigated factors that contribute to individual variability in warfarin dose. Furthermore, multivariate analysis was performed to investigate a warfarin dosing algorithm. RESULTS AND CONCLUSIONS: There were great inter-individual differences in warfarin maintenance dose in 259 patients, ranging from a minimum dose of 0.75 mg/day to a maximal dose of 8.00 mg/day. VKORC1 -1639 G>A polymorphism, body weight, age, and serum albumin were found to affect the inter-individual variability. The dosing algorithm of warfarin maintenance dose was investigated by multivariate linear regression. The regression equation was able to account for 33.2% (R(2)(Adj)=0.332) of the overall variability in warfarin dose.
INTRODUCTION: To establish individualized warfarin therapy, we investigated the contribution of genetic variations of vitamin K epoxide reductase complex subunit 1 gene (VKORC1) -1639 G>A and Cytochrome P450 2C9 gene (CYP2C9) and clinical factors on warfarin sensitivity in Japanese patients. MATERIALS AND METHODS: Genetic analyses of VKORC1 -1639 G>A and CYP2C9 2, 3, and 4 were performed in 259 Japanese patients and 341 healthy subjects. We selected 259 patients who have been prescribed warfarin with a 1.5-3.0 range of prothrombin time normalized as an international normalized ratio for at least 3 months and investigated factors that contribute to individual variability in warfarin dose. Furthermore, multivariate analysis was performed to investigate a warfarin dosing algorithm. RESULTS AND CONCLUSIONS: There were great inter-individual differences in warfarin maintenance dose in 259 patients, ranging from a minimum dose of 0.75 mg/day to a maximal dose of 8.00 mg/day. VKORC1 -1639 G>A polymorphism, body weight, age, and serum albumin were found to affect the inter-individual variability. The dosing algorithm of warfarin maintenance dose was investigated by multivariate linear regression. The regression equation was able to account for 33.2% (R(2)(Adj)=0.332) of the overall variability in warfarin dose.
Authors: Taewoo Lee; Andrea K Biddle; Sofia Lionaki; Vimal K Derebail; Sean J Barbour; Sameer Tannous; Michelle A Hladunewich; Yichun Hu; Caroline J Poulton; Shannon L Mahoney; J Charles Jennette; Susan L Hogan; Ronald J Falk; Daniel C Cattran; Heather N Reich; Patrick H Nachman Journal: Kidney Int Date: 2013-12-11 Impact factor: 10.612
Authors: Sherif M M Ekladious; Marianne Samir M Issac; Sahar Abd El-Atty Sharaf; Hazem S Abou-Youssef Journal: Mol Diagn Ther Date: 2013-12 Impact factor: 4.074
Authors: Erik Fung; Nikolaos A Patsopoulos; Steven M Belknap; Daniel J O'Rourke; John F Robb; Jeffrey L Anderson; Nicholas W Shworak; Jason H Moore Journal: Semin Thromb Hemost Date: 2012-10-06 Impact factor: 4.180