CAJ | 학술논문

目的建立针对中国汉族患者的华法林稳定剂量预测模型并验证其准确性.方法入选488例口服华法林抗凝的中国汉族患者,其目标国际标准化比值(INR)在1.5～3.0,且INR均稳定达标,抗凝指征包括人工瓣膜置换术后、心房颤动及肺血栓栓塞症.检测患者维生素K环氧化物还原酶复合体亚基1(VKORC1)、细胞色素P450 2C9(CYP2C9)及细胞色素P450 4F2(CYP4F2)基因多态性,记录患者平均每日华法林剂量、人口学信息及合并用药情况等;并将入选患者按入选的先后顺序分为建模组(323例)和验证组(165例).在建模组患者中,应用多元回归方法建立华法林稳定剂量预测模型;在验证组患者中,比较患者的实际剂量与预测剂量的差别,从而对模型的准确性进行初步验证.结果华法林稳定剂量预测模型包括VKORC1、CYP2C9、CYP4F2基因型,以及患者的年龄、体质量、身高、合并应用胺碘酮、地高辛等因素(该模型R2=0.652,P＜0.001);该模型在验证组患者中的平均预测剂量与患者的实际平均剂量差异无统计学意义[(3.51±1.03) mg比(3.53±1.41)mg,P=0.779],其中60.6％(100/165)的患者华法林预测剂量为理想预测剂量,17.6％(29/165)的患者华法林预测剂量过低,21.8％(36/165)的患者华法林预测剂量过高.结论基于VKORC1、CYP2C9和CYP4F2基因多态性的剂量预测模型可以帮助预测中国汉族患者华法林稳定剂量.
목적 건립침대중국한족환자적화법림은정제량예측모형병험증기준학성.방법 입선488례구복화법림항응적중국한족환자,기목표국제표준화비치(INR)재1.5～3.0,차INR균은정체표,항응지정포괄인공판막치환술후、심방전동급폐혈전전새증.검측환자유생소K배양화물환원매복합체아기1(VKORC1)、세포색소P450 2C9(CYP2C9)급세포색소P450 4F2(CYP4F2)기인다태성,기록환자평균매일화법림제량、인구학신식급합병용약정황등;병장입선환자안입선적선후순서분위건모조(323례)화험증조(165례).재건모조환자중,응용다원회귀방법건립화법림은정제량예측모형;재험증조환자중,비교환자적실제제량여예측제량적차별,종이대모형적준학성진행초보험증.결과 화법림은정제량예측모형포괄VKORC1、CYP2C9、CYP4F2기인형,이급환자적년령、체질량、신고、합병응용알전동、지고신등인소(해모형R2=0.652,P＜0.001);해모형재험증조환자중적평균예측제량여환자적실제평균제량차이무통계학의의[(3.51±1.03) mg비(3.53±1.41)mg,P=0.779],기중60.6％(100/165)적환자화법림예측제량위이상예측제량,17.6％(29/165)적환자화법림예측제량과저,21.8％(36/165)적환자화법림예측제량과고.결론 기우VKORC1、CYP2C9화CYP4F2기인다태성적제량예측모형가이방조예측중국한족환자화법림은정제량.
Objectives To establish an algorithm to predict the warfarin maintenance dose in Chinese Han population and validate the accuracy of this algorithm.Methods A total of 488 Chinese Han patients,hospitalized in Fuwai hospital and had a stable dose of warfarin and a target international normalized ratio(INR) of 1.5 to 3.0,were recruited.Indications for warfarin use included prosthetic heart valve,atrial fibrillation and pulmonary embolism.These patients were divided into derivation group (n =323) and validation group (n =165) according to the enrollment time.A warfarin maintenance dose algorithm was established based on genetic information,demographic characteristics and concomitant medications by multiple linear regression analysis in derivation group.In the validation group,we evaluated the accuracy of our algorithm by comparing the predicted dose with the actual dose.Results Our algorithm included VKORC1-1639G ＞ A,CYP2C9 * 3 and CYP4F2 genotype,age,Body hight,body weight,amiodarone and digoxin use(R2 =0.652,P ＜ 0.001).In the validation group,the average predicted dose by our algorithm had no statistical difference with the actual dose [(3.51 ± 1.03) mg vs.(3.53 ± 1.41) mg,P =0.779].Our algorithm identified 100 out of 165 (60.6％)patients in the validation group,whose predicted dose of warfarin was within 20％ of the actual dose,and predicted warfarin dose was underestimated in 17.6％ (29/165) patients and overestimated in 21.8％ (36/165) patients.Conclusion Our algorithm based on VKORC1,CYP2C9 and CYP4F2 polymorphisms can help to predict the warfarin maintenance dose in Chinese Han Population.