CYP2C19、ABCB1及PON1基因检测指导缺血性卒中患者氯吡格雷个体化用药-中国药房

CYP2C19、ABCB1及PON1基因检测指导缺血性卒中患者氯吡格雷个体化用药

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篇名：	CYP2C19、ABCB1及PON1基因检测指导缺血性卒中患者氯吡格雷个体化用药
TITLE：
摘要：	目的：利用CYP2C19、ABCB1及PON1基因检测结果指导缺血性卒中患者氯吡格雷个体化用药。方法：选取我院2016年11－12月收治的23例缺血性卒中患者，采用基于引物末端延伸的测序法（Sanger测序法）检测患者氯吡格雷相关基因（CYP2C1917、CYP2C193、CYP2C192、ABCB1及PON1）的基因型，临床药师根据基因类型提出给药建议。另选取1例反复缺血性卒中患者，测定氯吡格雷抑制率和血凝块形成的强度（MA）及上述氯吡格雷相关基因的基因型，为患者提供个体化的抗血小板治疗建议。结果：在23例患者中，CYP2C1917检测结果均为CC的野生型，其中CYP2C193检测结果为AG的突变杂合型1人，CYP2C192检测结果为AG的突变杂合型10人，此11人为中间代谢型，CYP2C192检测结果为AA的突变纯合型3人，为慢代谢型，上述14人建议停用氯吡格雷；余9人为正常代谢型，其中无ABCB1基因突变纯合型，PON1基因突变型6人，建议按正常剂量服用氯吡格雷。1例反复缺血性卒中患者2次检测氯吡格雷抑制率均为0，MA分别为66.4、68 mm，其ABCB1为突变杂合型，药物吸收减慢，CYP2C192为突变杂合型，PON1为突变杂合型，酶活性减弱，药物代谢减慢，建议停用氯吡格雷。结论：通过基因检测指导缺血性卒中患者氯吡格雷个体化用药，可达到患者脑卒中二级预防的目的，减少医疗资源浪费。
ABSTRACT：	OBJECTIVE： To utilize CYP2C19， ABCB1 and PON1 gene testing so as to guide individualized administration of clopidogrel in ischemic stroke patients. METHODS： Totally 23 patients with ischemic stroke were collected from our hospital during Nov.-Dec.， 2016. Genotype of clopidogrel related gene （CYP2C1917， CYP2C193， CYP2C192， ABCB1 and PON1） were determined by Sanger sequencing method. Clinical pharmacists provide suggestions according to genotype. A patient with recurrent ischemic stroke was collected. Inhibitory rate of clopidogrel， intensity of blood clot formation （MA） and the genotype of above clopidogrel related gene were determined. The suggestions about individualized anti-platelet therapy were provided for patients. RESULTS： Among 23 patients， CYP2C1917 was wild type of CC； among which CYP2C193 testing results were one person had mutant heterozygous type of AG； CYP2C192 testing result showed that 10 persons had mutant heterozygous type of AG， which were intermediate metabolic type； CYP2C192 testing result showed that 3 persons had mutation homozygous type of AA， which were slow metabolic type. 14 patients above were suggested to stop using clopidogrel. The remaining 9 patients were normal metabolic type， among which there was no mutant homozygous type of ABCB1 gene， and 6 persons were PON1 gene mutation type. It was recommended to take clopidogrel at normal dose. Inhibitory rate of clopidogrel was 0 in 2 times of testing for a patient with recurrent ischemic stroke， MA were 66.4 and 68 mm， ABCB1 was mutant heterozygous type， and drug absorption slowed down； CYP2C192 was mutant heterozygous type， PON1 was mutant heterozygous type. It was suggested that clopidogrel should be stopped by the reduction of enzyme activity and slowing down of drug metabolism. CONCLUSIONS： Gene detection guide individualized administration of clopidogrel in ischemic stroke patients so as to achieve secondary prevention of stroke and reduce waste of medical resources.
期刊：	2018年第29卷第19期
作者：	任晓蕾，张春燕，詹轶秋，黄琳，贺真，冯婉玉
AUTHORS：	REN Xiaolei，ZHANG Chunyan，ZHAN Yiqiu，HUANG Lin，HE Zhen，FENG Wanyu
关键字：	CYP2C19；PON1；ABCB1；氯吡格雷；缺血性卒中患者；个体化给药
KEYWORDS：	CYP2C19； PON1； ABCB1； Clopidogrel； Ischemic stroke patients； Individualized administration
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