Borgiani Paola, Ciccacci Cinzia, Forte Vittorio, Sirianni Elisabetta, Novelli Lucia, Bramanti Placido, Novelli Giuseppe
Department of Biopathology and Diagnostic Imaging, School of Medicine, Tor Vergata University, Rome, Italy.
Pharmacogenomics. 2009 Feb;10(2):261-6. doi: 10.2217/14622416.10.2.261.
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.
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 technology. Analysis of variance and multiple linear regression analyses were carried out to examine the contribution of genetic and nongenetic factors.
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.
Our data confirm and strengthen the role of this variant.
众所周知，华法林治疗存在问题，这是由于其治疗窗狭窄以及个体间差异极大。众多论文已表明细胞色素P450 2C9（CYP2C9）和维生素K环氧化物还原酶复合物亚基1（VKORC1）基因变异对这种差异有重要影响。最近，在美国发现细胞色素P450 4F2（CYP4F2）基因内的一个新单核苷酸多态性（SNP）与华法林剂量相关。
我们研究的目的是在意大利人群中重复这项研究，并评估新的CYP4F2变异相对于CYP2C9和VKORC1基因变异以及年龄和体重在解释华法林剂量差异方面的相对贡献。
采用TaqMan技术通过等位基因鉴别分析进行CYP4F2 rs2108622基因分型。进行方差分析和多元线性回归分析以检验遗传和非遗传因素的贡献。
我们的TT型患者每天需要5.49毫克，而CC型患者每天需要2.93毫克。方差分析表明，CYP4F2基因型可解释约7%的平均每周华法林剂量差异。我们包含CYP4F2、CYP2C9和VKORC1基因变异、年龄和体重的线性回归模型解释了60.5%的个体间差异。
我们的数据证实并强化了这一变异的作用。
