CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement
CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement
复制标题
DOI：
10.1111/j.1365-2125.2010.03698.x
复制
发表时间：
2010-08-01
影响因子：
3.4
通讯作者：
Zhao, Li-Zi
中科院分区：
文献类型：
--
作者：
Cen, Han-Jing;Zeng, Wu-Tao;Zhao, Li-Zi
目的探讨CYP 4F 2对中国汉族机械心脏瓣膜置换术（MHVR）患者华法林每日稳定剂量的影响。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对VKORC 1 3673 G>A、5417 G>T、CYP 2C 9 *3和CYP 4F 2 rs 2108622进行基因分型。直接测序法检测VKORC 1 9041 G>A基因多态性。使用多元线性回归分析来研究CYP 4F 2 rs 2108622 CT/TT组服用的稳定华法林剂量（3.2 mg/d（-1））显著高于CC组（2.9 mg/d（-1），95% CI 0.2，1.0，P = 0.033）。多元线性回归模型包括VKORC 1 3673 G>A、CYP 2C 9、CYP 4F 2基因型和临床特征。该模型可以解释中国汉族MHVR患者稳定华法林剂量的56.1%的方差。CYP 4F 2对华法林剂量变异的贡献约为4%。VKORC 1 5417 G> T的SNPs没有变化。结论CYP 4F 2是中国汉族MHVR患者华法林稳定剂量个体差异的次要显著因素。CYP 2C 9和VKORC 1基因型对华法林稳定剂量变异性的影响也得到了证实。
AIMSThe objective of this study was to assess the effect of the CYP4F2 on the daily stable warfarin dose requirement in Han Chinese patients with mechanical heart valve replacement (MHVR).METHODSFrom March 2007 to November 2008, 222 Han Chinese MHVR patients were recruited in our study. VKORC1 3673G>A, 5417G>T, CYP2C9*3 and CYP4F2 rs2108622 were genotyped by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Polymorphisms of VKORC1 9041G>A were detected by direct sequencing. Multiple linear regression analysis was used to investigate the contribution of CYP4F2.RESULTSThe CYP4F2 rs2108622 CT/TT group took a significantly higher stable warfarin dose (3.2 mg day(-1)) than the CC group (2.9 mg day(-1), 95% CI 0.2, 1.0, P = 0.033). The multiple linear regression model included VKORC1 3673G>A, CYP2C9, CYP4F2 genotypes and clinical characteristics. The model could explain 56.1% of the variance in stable warfarin dose in Han Chinese patients with MHVR. CYP4F2 contributed about 4% to the variance in the warfarin dose. There was no variation in the SNPs of VKORC1 5417G>T.CONCLUSIONCYP4F2 is a minor significant factor of individual variability in the stable warfarin dose in Han Chinese patients with MHVR. The effect of CYP2C9 and VKORC1 genotypes on variability in the stable warfarin dose had also been confirmed.