DNA测序法检测CYP2C19基因多态性指导氯吡格雷用药的临床价值

Clinical value of DNA sequencing for CYP2C19 polymorphisms detection on the application of clopidogrel

目的评估DNA测序法检测细胞色素氧化酶P450 2C19(CYP2C19)多态性以指导氯吡格雷临床用药。方法选取2010年11月至2013年11月武汉大学人民医院心血管内科诊断为急性冠状动脉综合征,并首次接受经皮冠状动脉介入治疗术(PCI)的140例患者为研究对象,随机分为试验组及对照组各70例。试验组采集外周血标本并提取基因组DNA,根据已知的CYP2C19基因序列,设计针对CYP2C19*2、CYP2C19*3位点的特异性引物,聚合酶链反应扩增包含CYP2C19基因多态性位点的DNA片段;并以DNA测序法进行鉴定,分析不同CYP2C19基因型在试验组患者中的分布频率。对照组患者使用氯吡格雷药物但未检测相关基因。比较两组患者随访过程中发生冠状动脉血栓事件的差异。结果 DNA测序结果显示,试验组中共有4种基因型组合被检测到:*1/*1(636GG,681GG)、*1/*2(636GG,681GA)、*2/*2(636GG,681AA)、*1/*3(636GA,681GG),分布频率分别为33例(47.1%)、29例(41.4%)、4例(5.7%)、4例(5.7%),而*3/*3(636AA,681GG)和*2/*3(636GA,681GA)未检测到。经基因型指导氯吡格雷用药的试验组患者发生支架冠状动脉血栓事件的比例为0.0%,明显低于对照组的7.1%,差异有统计学意义(P<0.05)。结论基因型指导氯吡格雷用药有助于患者用药剂量的调整,可降低冠状动脉血栓事件的发生率。

Objective To evaluate the clinical application value of detectiing Cytochrome P450 2C19（CYP2C19）polymorphisms by DNA sequencing in clopidogrel application.Methods From November 2010 to November 2013,a total of 140 blood samples were randomly collected in patients with acute coronary syndrome and treated with percutaneous coronary intervention（PCI）for the first time in the department of cardiology in People′s Hospital of Wuhan University.Aaa the patients were divided as control group and study group randomly,70 patients in each group.According to known gene sequences of CYP2C19,specific primers were synthesized to genotype the CYP2C19＊2and CYP2C19＊3alleles through polymerase chain reaction（PCR）amplification and DNA sequencing.Meanwhile,the distribution of these alleles in the study group was analyzed.The control group didn′t do genotype but use clopidogrel.The incidence rates of coronary artery thrombosis in the process of follow-up between the two groups was compared.Results DNA sequencing results showed that 4kinds of gene type were detected including ＊1/＊1（636GG,681GG）,＊1/＊2（636GG,681GA）,＊2/＊2（636GG,681AA）and ＊1/＊3（636GA,681GG）.The distribution rates of them were 47.1%,41.4%,5.7% and 5.7%respectively.However,＊3/＊3（636AA,681GG）and＊2/＊3（636GA,681GA）were not found.Besides,the incidence rate of coronary artery thrombosis in the study group（0.0%）was significant lower than that of the control group（7.1%）（P0.05）.Conclusion It is help to use the detection of CYP2C19 polymorphism by DNA sequencing guiding the dosage of clopidogrel,and could reduce the occurrence of coronary artery thrombosis.