贵州地区基因分型指导下非瓣膜性房颤患者华法林预测模型的建立

Establishment of Warfarin predictive model for NVAF patients under the guidance of genotyping in Guizhou

目的研究贵州地区非瓣膜性房颤(NVAF)患者的维生素K环氧化物还原酶复合体1(VKORC1)和细胞色素P4502C9(CYP2C9)基因多态性对华法林稳定剂量的影响,并构建华法林预测模型,为临床个体化给药提供依据。方法根据设定标准选取贵阳市第二人民医院心内科150名NVAF患者,对纳入的患者进行全血DNA提取,采用荧光PCR技术检测患者的VKORC1和CYP2C9的基因多态性,并结合患者身高、体质量、性别、年龄等临床特征,运用统计学对这些因素进行相关性分析,采用多元线性回归法建立华法林稳定剂量预测模型公式。结果纳入的150名患者中,VKORC1基因型检测结果中AA型117例(78.00%),GA型31例(20.67%),GG型2例(1.33%),CYP2C9基因型检测结果中AA型133例(88.67%),AC型17例(11.33%),CC型0例(0.00%)。不同VKORC1和CYP2C9基因型患者华法林稳定剂量有统计学意义。预测模型:D=6.843+0.190×民族-0.058×年龄-0.024×体重-1.033×CYP2C9+0.719×VKORC1。结论贵州地区服用华法林的NVAF患者中,存在VKORC1和CYP2C9的基因多态性差异,通过构建华法林稳定剂量预测模型,可在一定程度上解释这些差异,并较为准确的指导临床用药。

Objective To investigate the influence of VKORC1 and CYP2C9 in Guizhou population on the dose of stable Warfarin and establish a predictive dose model that can provide evidence for individualized drug administration in clinic.Methods According to the standards set,150 NVAF patients were selected in cardiology of Guiyang Second People’s Hospital.The whole blood DNA was extracted from the included patients,and the patient’s polymorphism of VKORC1 and CYP2C9 was tested by fluorescent PCR.Clinical features such as height,weight,sex and age were combined,statistical analysis was used to analyze the correlation of these factors,Warfarin’s stable dose prediction model was built by multiple linear regression method.Results Among 150 patients,VKORC1 genotyping showed that there were 117 cases(78.00%)of AA type,31(20.67%)of AG type and 2(1.33%)of GG type.CYP2C9 genotyping showed that the frequency of AA,AC,CC was 133(88.67%),17(11.33%),0(0.00%).Stable doses of Warfarin in patients with different genotypes of VKORC1 and CYP2C9 were statistically significant.The predictive model:D=6.843+0.190×Ethnicity-0.058×Age-0.024×Weight-1.033×CYP2C9+0.719×VKORC1.Conclusion Among NVAF patients taking Warfarin in Guizhou,there are differences in gene polymorphism of VKORC1 and CYP2C9.The establishment of Warfarin stable dose prediction model can explain these differences to a certain extent and provide more accurate guidance for clinical medication.