VKORC1-1639 G/A、CYP2C93*基因多态性对华法林使用剂量的影响

Influence of VKORC1-1639 G/A, CYP2C93* Polymorphism on Warfarin Dose

关键词:  华法林  血栓疾病  维生素K环氧化物还原酶复合物1  细胞色素P450酶2C9  基因多态性  个体差异  药学服务

Key words:  warfarin  thrombotic disease  vitamin K epoxide reductase complex 1  cytochrome P450 enzyme 2C9  gene polymorphism  individual differences  pharmaceutical care

摘要:

目的 基于VKORC1-1639 G/A及CYP2C93^*的基因多态性初步探讨华法林的使用剂量。方法 收集2016年10月-2018年2月进行华法林用药指导相关基因检测的100例患者，记录患者基本信息（身高、体质量等）。采用数字荧光分子杂交检测VKORC1-1639 G/A，CYP2C93^*的基因型分布，并结合患者年龄、身高、体质量等，根据国际华法林药物基因组学联合会（IWPC）公式计算患者华法林理论剂量。结果 VKORC1-1639 G/A AA、AG、GG基因型实际频率分别为84%，15%，1%；等位基因A，G频率分别为91.5%，8.5%。CYP2C9 3^* AA型、AC型、CC型实际频数分别为91%，9%，0%；等位基因A，C频率分别为95.5%，4.5%。不同VKORC1-1639 G/A、CYP2C93^*基因型华法林理论用量不同，VKORC1-1639 G/A AA型并CYP2C93^* AA型和VKORC1-1639 G/A AG型并CYP2C93^* AA型患者华法林剂量均高于VKORC1-1639 G/A AA型并CYP2C93^* AC型患者；VKORC1-1639 G/A AG型并CYP2C93^* AA型患者华法林用量高于VKORC1-1639 G/A AA型并CYP2C93^* AA型患者，3组间两两比较，差异有统计学意义（P<0.05）。结论 华法林代谢相关基因的基因多态性为VKORC1-1639 G/A AA及CYP2C93^* AA型占多数，表明VKORC1-1639 G/A基因突变率高，CYP2C93^*基因突变率较低，且两者多态性影响个体间华法林的理论剂量。

Abstract:

OBJECTIVE To investigate the use of warfarin on the basis of gene polymorphisms of VKORC1-1639 G/A and CYP2C93^*. METHODS The 100 patients from October 2016 to February 2018 for warfarin guidelines related to genetic testing were collected, recorded patients basic information (height, weight, etc.). The genotype distribution of VKORC1-1639 G/A and CYP2C93^* was detected by digital fluorescent molecular hybridization(DFMH1), and the initial dose of warfarin was calculated according to the formula of international warfarin pharmacogenomics federation (IWPC) combined with the patien's age, height and weight. RESULTS The actual frequencies of VKORC1-1639 G/A AA, AG and GG genotypes were 84%, 15% and 1% respectively, frequencies of allele A and G were 91.5% and 8.5%. The actual frequencies of CYP2C9 3^* AA, AC and CC were 91%, 9% and 0% respectively, frequencies of allele A and C were 95.5% and 4.5%. Different VKORC1-1639G/A, CYP2C93^* genotype warfarin dosage was different, warfarin dosage was higher in the two group of VKORC1-1639G/A AA & CYP2C93^* AA and VKORC1-1639G/A AG & CYP2C93^* AA, than VKORC1-1639 G/A AA & CYP2C93^* AC group. Warfarin dosage was higher in the group of VKORC1-1639 G/A AA & CYP2C93^* AA, than VKORC1-1639 G/A AG & CYP2C9*1/*1 group, and the differences were statistically significant(P<0.05). CONCLUSION The majority of warfarin metabolic related genes are VKORC1-1639 G/A AA & CYP2C93^* AA group, indicating high mutation rate of VKORC1-1639 G/A. The mutation rate of CYP2C93^* is low, and its polymorphism affects the dose of warfarin among individuals.