Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Br J Clin Pharmacol. 2011 Sep;72(3):442-50. doi: 10.1111/j.1365-2125.2011.03942.x.
To investigate the influence of polymorphisms in CYP2C9, VKORC1, CYP4F2 and F2 genes on warfarin dose-response and develop a model including genetic and non-genetic factors for warfarin dose prediction needed for each patient.
A total of 279 patients of European ancestry on warfarin medication were investigated. Genotypes for -1639G>A, 1173C>T, and 3730G>A SNPs in the VKORC1 gene, CYP2C92 and CYP2C93, 1347C>T in the CYP4F2 gene and 494C>T in the F2 gene were determined by allelic discrimination with Taqman 5'-nuclease assays.
The CYP2C92 and CYP2C93 polymorphisms in the CYP2C9 gene, -1639G>A and 1173C>T in the VKORC1 gene and 494C>T in the F2 gene are responsible for lower anticoagulant doses. In contrast, 1347C>T in the CYP4F2 gene and 3730G>A in the VKORC1 gene are responsible for higher doses of warfarin. An algorithm including genetic, biological and pharmacological factors that explains 63.3% of warfarin dose variation was developed.
The model suggested has one of the highest coefficients of determination among those described in the literature.
研究 CYP2C9、VKORC1、CYP4F2 和 F2 基因多态性对华法林剂量反应的影响，并建立一个包含遗传和非遗传因素的模型，以预测每个患者所需的华法林剂量。
共调查了 279 名接受华法林治疗的欧洲血统患者。通过 Taqman 5'-核酸酶检测法，对 VKORC1 基因的-1639G>A、1173C>T 和 3730G>A SNPs、CYP2C92 和 CYP2C93 多态性、CYP4F2 基因中的 1347C>T 和 F2 基因中的 494C>T 进行了基因分型。
CYP2C9 基因中的 CYP2C92 和 CYP2C93 多态性、VKORC1 基因中的-1639G>A 和 1173C>T 以及 F2 基因中的 494C>T 与较低的抗凝剂量相关。相反，CYP4F2 基因中的 1347C>T 和 VKORC1 基因中的 3730G>A 与华法林的较高剂量相关。开发了一种包含遗传、生物学和药理学因素的算法，该算法可以解释 63.3%的华法林剂量变化。
该模型具有文献中描述的最高决定系数之一。
