Effect of VKORC1 –1639 G>A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients
| Autor: | Sonoko Sakawa, Hideki Hayashi, Misa Yoshizawa, Yoshio Tashiro, Yoshinori Kawarasaki, Kazuyuki Inoue, Hideaki Moriwaki, Takehide Akimoto, Osamu Doi, Midori Kimura, Kunihiko Itoh |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype medicine.drug_class Serum albumin Pharmacology Biology Gastroenterology Mixed Function Oxygenases Gene Frequency Japan Vitamin K Epoxide Reductases Internal medicine medicine Humans CYP2C9 Alleles Serum Albumin Aged Cytochrome P-450 CYP2C9 Retrospective Studies Aged 80 and over Prothrombin time Polymorphism Genetic medicine.diagnostic_test Maintenance dose Body Weight Anticoagulant Warfarin Anticoagulants Hematology Middle Aged Linear Models biology.protein Female Vitamin K epoxide reductase Aryl Hydrocarbon Hydroxylases VKORC1 Algorithms medicine.drug |
| Zdroj: | Thrombosis Research. 124:161-166 |
| ISSN: | 0049-3848 |
| DOI: | 10.1016/j.thromres.2008.11.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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