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中国患者中与CYP2C9和VKORC1基因多态性相关的华法林剂量反应变异性。

Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients.

作者信息

Ye Changqing, Jin Haiqiang, Zhang Rui, Sun Yongan, Wang Zhaoxia, Sun Weiping, Sun Wei, Peng Qing, Liu Ran, Huang Yining

机构信息

Department of Neurology, Peking University First Hospital, Beijing, China.

出版信息

J Int Med Res. 2014 Feb;42(1):67-76. doi: 10.1177/0300060513499094. Epub 2013 Nov 28.

Abstract

OBJECTIVE

To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 (VKORC1)-1639 G > A polymorphisms in Chinese patients receiving warfarin therapy.

METHODS

Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated.

RESULTS

Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C911 and CYP2C913 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.87 ± 0.14) than those with the VKORC1-1639 AG genotype (1.32 ± 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 ± 0.70 mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 ± 0.70 mg/day).

CONCLUSIONS

Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.

摘要

目的

研究接受华法林治疗的中国患者中细胞色素P450 2C9(CYP2C9)基因变异及维生素K环氧化物还原酶复合体亚单位1(VKORC1)-1639G>A多态性的发生率及其意义。

方法

连续纳入需要口服华法林治疗的中国汉族患者。研究CYP2C9 *1、*2、*3、*4、*5基因变异及VKORC1-1639G>A多态性与第4天国际标准化比值(INR)和华法林维持剂量之间的相关性。

结果

101例患者中,CYP2C9 11和CYP2C9 13基因型患者第4天INR或华法林每日维持剂量无显著差异。VKORC1-1639 AA基因型患者第4天INR(1.87±0.14)高于VKORC1-1639 AG基因型患者(1.32±0.15)。VKORC1-1639 AA基因型患者的华法林维持剂量(2.40±0.70mg/天)显著低于VKORC1-1639 AG基因型患者(4.83±0.70mg/天)。

结论

与白种人群不同,中国人群中VKORC1-1639G>A多态性可能是与华法林反应变异性相关的主要遗传因素。

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