两种华法林剂量预测模型在老年房颤患者中的验证与评价  

Validation and evaluation of two warfarin dose prediction models in elderly patients with atrial fibrillation

作　　者：阮富旺 刘伟畴 李凤珍 阮林婷 陈波 陈小珑 RUAN Fuwang;LIU Weichou;LI Fengzhen;RUAN Linting;CHEN Bo;CHEN Xiaoong(Department of Clinical Laboratory,Dongguan Guanghua Hospital,Dongguan,Guangdong,China,523000;Department of Clinical Laboratory,Dongguan Peoples Hospital,Dongguan,Guangdong,China,52300;Department of Gastroenterology,Dongcheng Hospital,Dongguan,Guangdong,China,523000;DAAN Gene Co.,Ltd.,Guangzhou,Guangdong,China,510665)

机构地区：[1]东莞光华医院检验科,广东东莞523000 [2]东莞市人民医院检验科,广东东莞523000 [3]东莞市东城医院消化内科,广东东莞523000 [4]广州达安基因股份有限公司,广东广州510665

出　　处：《分子诊断与治疗杂志》2023年第11期1981-1985,共5页Journal of Molecular Diagnostics and Therapy

基　　金：东莞市社会发展科技项目(20211800903482)。

摘　　要：目的 验证两种基于VKORC1和CYP2C9基因单核苷酸多态性的华法林给药模型的准确性。方法 收集在东莞光华医院就诊并服用华法林抗凝治疗且国际标准化比值(INR)达到目标范围2.0~3.0的83例年龄≥75岁汉族老年房颤患者的临床资料,采用PCR-荧光探针法分析CYP2C9*3和VKORC1-1639A>G位点的单核苷酸多态性,代入模型预测华法林剂量,比较预测剂量的准确性及与实际稳定剂量的相关性,分析影响华法林剂量的因素。结果 83例患者CYP2C9*1/*1基因型频率90.36%,*1/*3基因型频率9.64%;VKORC1-1639A/A基因型频率73.49%,A/G基因型频率26.51%。模型1预测剂量与实际稳定剂量的相关性(R~2=0.477)高于模型2(R~2=0.385),预测剂量的差异有统计学意义(t=2.691,P<0.05)。模型1预测的剂量在理想预测剂量范围内人数占比59.03%,高于模型2的53.01%。模型1与实际稳定剂量的差值在95%CI以外的概率为3.22%,小于模型2的7.22%。CYP2C9*1/*1型患者实际稳定剂量(3.02±0.67)mg/d高于*1/*3型患者的(2.37±0.48)mg/d,VKORC1-1639 A/A型患者华法林实际稳定剂量(2.72±0.55)mg/d低于A/G型的(3.61±0.56)mg/d,未合用胺腆酮患者华法林稳定剂量(3.00±0.67)mg/d高于合用胺腆酮的(2.29±0.35)mg/d,男性患者华法林稳定剂量(3.09±0.69)mg/d高于女性患者的(2.68±0.57)mg/d,差异均有统计学意义(t=2.684、-6.462、2.306、2.696,P均<0.05)。是否吸烟及合用阿司匹林,华法林实际稳定剂量的差异均无统计学意义(P>0.05)。结论 华法林使用剂量个体差异受CYP2C9和VKORC1基因单核苷酸多态性和非遗传因素的影响,模型1可能更适用于本地区老年房颤患者的华法林剂量预测。Objective To validate the accuracy of two warfarin dosing models based on VKORC1 and CYP2C9 gene polymorphisms.Methods Clinical data was collected from 83 elderly Han patients aged≥75 years old with atrial fibrillation at Dongguan Guanghua Hospital,who were treated with oral warfarin and achieved the target range of international normalized ratio(INR)2.0~3.0.Genetic polymorphisms of CYP2C9*3 and VKORC1-1639A>G loci were analyzed using PCR-fluorescent probe.Model 1 and model 2 were employed to predict the warfarin dose.The accuracy of the predicted dose and its correlation with the actual stable dose were compared,and the factors affecting the actual stable dose were analyzed.Results In the cohort of 83 patients,the frequency of CYP2C9*1/*1 genotype was 90.36%,while*1/*3 genotype was 9.64%.The VKORC1-1639A/A genotype was present in 73.49%of the cases,and the A/G genotype was found in 26.51%.Regarding the predictive models,model 1 demonstrated a higher correlation(R2=0.477)between predicted and actual stable doses compared to model 2(R2=0.385).The difference in the predicted dose was statistically significant(t=2.691,P<0.05).Model 1 accurately predicted the ideal dose range for 59.03%of the population,outperforming model 2,which achieved this for only 53.01%.The probability of the difference between model 1 and the actual stable dose lying beyond the 95%confidence interval was found to be 3.22%,which was less than 7.22%in model 2.The actual stable dose of warfarin was higher in CYP2C9*1/*1 patients(3.02±0.67)mg/d compared to*1/*3 patients(2.37±0.48)mg/d.In VKORC1-1639A/A patients,the stable dose(2.72±0.55)mg/d was lower than that in A/G patients(3.61±0.56)mg/d.Furthermore,patients without the combined use of amiodarone had a higher stable dose(3.00±0.67)mg/d than those with amiodarone co-administration(2.29±0.35)mg/d.Additionally,the stable dose of warfarin was also higher in male patients(3.09±0.69)mg/d than in female patients(2.68±0.57)mg/d.These observed differences were statistically significant(t=2.6

关 键 词：心房颤动 华法林 单核苷酸多态性 CYP2C9 VKORC1 

分 类 号：R541.75[医药卫生—心血管疾病]