Ye Changqing, Jin Haiqiang, Zhang Rui, Sun Yongan, Wang Zhaoxia, Sun Weiping, Sun Wei, Peng Qing, Liu Ran, Huang Yining
Department of Neurology, Peking University First Hospital, Beijing, China.
J Int Med Res. 2014 Feb;42(1):67-76. doi: 10.1177/0300060513499094. Epub 2013 Nov 28.
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.
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.
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).
Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.
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。
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。
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)。
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。