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用于预测印度患者稳定维持剂量的华法林剂量模型

Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients.

作者信息

Gaikwad Tejasvita, Ghosh Kanjaksha, Avery Peter, Kamali Farhad, Shetty Shrimati

机构信息

1 National Institute of Immunohaematology (ICMR), Department of Thrombosis and Haemostasis, KEM Hospital, Parel, Mumbai, India.

2 Surat Raktadan Kendra & Research Centre, Regional Blood Transfusion Centre, Surat, Gujarat, India.

出版信息

Clin Appl Thromb Hemost. 2018 Mar;24(2):353-359. doi: 10.1177/1076029616683046. Epub 2017 Jan 4.

Abstract

The main aim of this study was to screen various genetic and nongenetic factors that are known to alter warfarin response and to generate a model to predict stable warfarin maintenance dose for Indian patients. The study comprised of 300 warfarin-treated patients. Followed by extensive literature review, 10 single-nucleotide polymorphisms, that is, VKORC1-1639 G>A (rs9923231), CYP2C92 (rs1799853), CYP2C93 (rs1057910), FVII R353Q (rs6046), GGCX 12970 C>G (rs11676382), CALU c.4A>G (rs1043550), EPHX1 c.337T>C (rs1051740), GGCX: c.214+597G>A (rs12714145), GGCX: 8016G>A (rs699664), and CYP4F2 V433M (rs2108622), and 5 nongenetic factors, that is, age, gender, smoking, alcoholism, and diet, were selected to find their association with warfarin response. The univariate analysis was carried out for 15 variables (10 genetic and 5 nongenetic). Five variables, that is, VKORC1-1639 G>A, CYP2C92, CYP2C9*3, age, and diet, were found to be significantly associated with warfarin response in univariate analysis. These 5 variables were entered in stepwise and multiple regression analysis to generate a prediction model for stable warfarin maintenance dose. The generated model scored R of .67, which indicates that this model can explain 67% of warfarin dose variability. The generated model will help in prescribing more accurate warfarin maintenance dosing in Indian patients and will also help in minimizing warfarin-induced adverse drug reactions and a better quality of life in these patients.

摘要

本研究的主要目的是筛选各种已知会改变华法林反应的遗传和非遗传因素,并建立一个模型来预测印度患者稳定的华法林维持剂量。该研究纳入了300名接受华法林治疗的患者。在进行广泛的文献综述后,选择了10个单核苷酸多态性,即VKORC1 - 1639 G>A(rs9923231)、CYP2C92(rs1799853)、CYP2C93(rs1057910)、FVII R353Q(rs6046)、GGCX 12970 C>G(rs11676382)、CALU c.4A>G(rs1043550)、EPHX1 c.337T>C(rs1051740)、GGCX: c.214 + 597G>A(rs12714145)、GGCX: 8016G>A(rs699664)以及CYP4F2 V433M(rs2108622),和5个非遗传因素,即年龄、性别、吸烟、酗酒和饮食,以找出它们与华法林反应的关联。对15个变量(10个遗传变量和5个非遗传变量)进行了单因素分析。在单因素分析中,发现5个变量,即VKORC1 - 1639 G>A、CYP2C92、CYP2C9*3、年龄和饮食,与华法林反应显著相关。将这5个变量纳入逐步回归和多元回归分析,以生成稳定华法林维持剂量的预测模型。生成的模型R值为0.67,这表明该模型可以解释67%的华法林剂量变异性。生成的模型将有助于为印度患者开出更准确的华法林维持剂量,也有助于减少华法林引起的药物不良反应,并改善这些患者的生活质量。

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