CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population
CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population
复制标题
DOI：
10.2217/14622416.10.2.261
复制
发表时间：
2009-02-01
期刊：
影响因子：
2.1
通讯作者：
Novelli, G.
中科院分区：
文献类型：
--
作者：
Borgiani, P.;Ciccacci, C.;Novelli, G.
简介：众所周知，华法林治疗是有问题的，因为它的治疗范围窄，个体间差异大。许多论文已经显示了CYP 2C 9和VKORC 1遗传变异对这种变异性的重要贡献。最近，在美国发现CYP 4F 2基因内的一个新的SNP与华法林剂量相关。目的：我们工作的目的是在意大利人群中重复这项研究，并评估新的CYP 4F 2变异体在解释华法林剂量变异性方面的相对贡献，涉及CYP 2C 9和VKORC 1遗传变异体以及年龄和体重。材料与方法：采用TaqMan（R）技术，通过等位基因鉴别分析进行CYP 4F 2 rs 2108622基因分型。进行方差分析和多元线性回归分析，以检查遗传和非遗传因素的贡献。结果：我们的TT患者需要5.49 mg/天，而CC患者需要2.93 mg/天。方差分析表明，约7%的平均每周华法林剂量方差是由CYP 4F 2基因型解释。我们的线性回归模型包括CYP 4F 2，CYP 2C 9和VKORC 1遗传变异，年龄和体重，解释了60.5%的个体间变异。结论：我们的数据证实并加强了这种变异的作用。
Introduction: It is known that warfarin treatment is problematic, due to its narrow therapeutic range and to the great interindividual variability. Numerous papers have shown the important contribution of CYP2C9 and VKORC1 genetic variants to this variability. Recently, a new SNP within the CYP4F2 gene was found associated with warfarin dose in the USA. Aims: The aim of our work was to replicate this study in the Italian population and to assess the new CYP4F2 variant relative contribution in explaining warfarin dose variability with respect to CYP2C9 and VKORC1 genetic variants together with age and weight. Materials & methods: CYP4F2 rs2108622 genotyping was performed by allelic discrimination assay by TaqMan (R) technology. Analysis of variance and multiple linear regression analyses were carried out to examine the contribution of genetic and nongenetic factors. Results: Our TT patients require 5.49 mg/day versus 2.93 mg/day of our CC patients. Analysis of variance indicates that about 7% of mean weekly warfarin dose variance is explained by CYP4F2 genotype. Our linear regression model including CYP4F2, CYP2C9 and VKORC1 genetic variants, age and weight, explains 60.5% of the interindividual variability. Conclusion: Our data confirm and strengthen the role of this variant.