CYP2C9及VKORC1基因多态性对心脏瓣膜置换术后华法林抗凝治疗策略的影响

doi:10.3969/j.issn.1673-8640.2019.02.007

摘要/Abstract

摘要：

目的评价CYP2C9及VKORC1基因多态性检测对心脏瓣膜置换术后华法林抗凝治疗策略的影响。方法随机选取380例心脏瓣膜置换术患者,190例行CYP2C9和VKORC1基因多态性检测（基因检测组）,另190例不作相关检测（对照组）,记录患者服用华法林稳定剂量、国际标准化比值（INR）达标时间和住院时间。结果 190例行基因多态性检测的患者中CYP2C9 *1/*1型 170例（89.5%）,*1/*3型19例（10.0%）,*3/*3型 1例（0.5%）;VKORC1 AA型155例（81.6%）,AG型35例（18.4%）,未检出GG型。基因检测组INR达标时间[（4.0±1.7）d]低于对照组[（4.6±2.1）d]（P<0.01）,2个组住院时间差异无统计学意义（P>0.05）。结论 CYP2C9及VKORC1基因多态性检测对于抗凝治疗初期临床策略的制定起重要作用,可缩短患者INR达标时间,有助于减少患者出血及栓塞风险。

关键词: 华法林, CYP2C9, VKORC1, 基因多态性, 心脏瓣膜置换

Abstract:

Objective To evaluate the influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin anticoagulation strategy after cardiac valve replacement. Methods A total of 380 patients undergoing cardiac valve replacement were enrolled randomly,CYP2C9 and VKORC1 gene polymorphisms in 190 cases were detected（gene polymorphism detection group）,and the other 190 cases were used as control group. The warfarin stable dose,the time to reach therapeutic international normalized ratio（INR） and hospitalization time were recorded. Results There were 170 cases of *1*1（89.5%）,19 cases of *1*3（10.0%） and 1 case of *3*3（0.5%） in CYP2C9,and 155 cases（81.6%） had AA,and 35 cases（18.4%） had AG in VKORC1. There was no case with GG. The time to reach therapeutic INR of gene polymorphism detection group [（4.0±1.7）d] was shorter than that of control group [（4.6±2.1）d]（P<0.01）. There was no statistical significance for hospitalization time between the 2 groups（P>0.05）. Conclusions CYP2C9 and VKORC1 gene polymorphism detection plays a role for early clinical anticoagulation strategy,which can shorten the time to reach therapeutic INR and reduce hemorrhage and embolism risk.

Key words: Warfarin, CYP2C9, VKORC1, Gene polymorphism, Cardiac valve replacement

中图分类号:

R446.1

蒿叶霞, 郑璇, 胡元萍, 张李涛, 颜新生, 曹树正, 王章, 张真路. CYP2C9及VKORC1基因多态性对心脏瓣膜置换术后华法林抗凝治疗策略的影响[J]. 检验医学, 2019, 34(2): 126-129.

HAO Yexia, ZHENG Xuan, HU Yuanping, ZHANG Litao, YAN Xinsheng, CAO Shuzheng, WANG Zhang, ZHANG Zhenlu. Influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin anticoagulation strategy after cardiac valve replacement[J]. Laboratory Medicine, 2019, 34(2): 126-129.

图/表 2

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基因型	例数	华法林（mg/d）	INR达标时间（d）	住院时间（d）
CYP2C9*3
1/1	170	2.5±0.9	3.8±1.7	18.2±4.6
1/3	19	2.0±0.9	4.9±1.8	16.9±3.6
P值		0.020	0.010	0.252
VKORC1
AA	155	2.3±0.8	3.8±1.6	18.1±4.7
AG	35	3.1±1.1	4.8±1.7	18.1±4.0
P值		<0.01	<0.01	0.966

基因型	例数	华法林（mg/d）	INR达标时间（d）	住院时间（d）
CYP2C9*3
1/1	170	2.5±0.9	3.8±1.7	18.2±4.6
1/3	19	2.0±0.9	4.9±1.8	16.9±3.6
P值		0.020	0.010	0.252
VKORC1
AA	155	2.3±0.8	3.8±1.6	18.1±4.7
AG	35	3.1±1.1	4.8±1.7	18.1±4.0
P值		<0.01	<0.01	0.966

组别	例数	华法林（mg/d）	INR达标时间（d）	住院天数（d）
基因检测组	190	2.4±0.9	4.0±1.7	18.1±4.5
对照组	190	2.3±1.0	4.6±2.1	19.0±6.5
P值		0.178	<0.01	0.107

组别	例数	华法林（mg/d）	INR达标时间（d）	住院天数（d）
基因检测组	190	2.4±0.9	4.0±1.7	18.1±4.5
对照组	190	2.3±1.0	4.6±2.1	19.0±6.5
P值		0.178	<0.01	0.107