缺血性脑血管病患者CYP2C19基因多态性的相关性研究

Association of CYP2C19 gene polymorphisms in patients with ischemic cerebrovascular disease

目的探讨缺血性脑血管病(ischemic cerebrovascular disease,ICVD)患者CYP2C19基因单核苷酸多态性(single nucleotide polymorphism,SNP)与临床特征、治疗效果之间的关系。为脑血管疾病患者服用抗血小板药物的个体化治疗提供参考依据。方法昆明医科大学第一附属医院神经外科2015年1月—2017年4月间完善CYP2C19(*2、*3、*17)基因检测的153例患者作为研究对象。将所有患者分别按每个基因位点基因检测的结果分为突变组及非突变组,分析CYP2C19基因各位点突变与患者临床特征、缺血性脑血管病发病及服药后发生缺血事件的关系。结果本组153例患者中,男70例(45.8%),女83例(54.2%),平均年龄(53.2±11.6)岁;CYP2C19(*2、*3、*17)各位点基因型突变的频率分别为53.6%、9.2%及2.0%。CYP2C19*2位点突变与非突变组患者的吸烟、饮酒比率及血胆固醇(TC)、低密度脂蛋白胆固醇含量比较,差异均有统计学意义(P<0.05-0.01);CYP2C19*3位点突变与非突变组患者的血高密度脂蛋白胆固醇含量的差异有统计学意义(P<0.005)。CYP2C193个位点突变与与非突变组患者发生ICVD的差异均无统计学意义(均P>0.05)。CYP2C19*2位点突变患者服药后的缺血事件发生率比非突变患者明显增加(P<0.05)。结论 患者是否患有ICVD与CYP2C19(*2、*3、*17)基因位点多态性无明显关系;抗血小板治疗后是否发生缺血性事件与CYP2C19*2基因位点突变有关。因CYP2C19*2基因的突变率较高(本组患者达53.6%),建议患者服抗血小板药前先行基因检测,以避免可能预后不佳。

Objective To investigate whether the single nucleotide polymorphism ( SNP) of CYP2C19 gene in patients with ischemic cerebrovascular disease ( ICVD) is related to the clinical characteristics, ICVD, and therapeutic efficacy.To provide the evidence to make an individualized anti-platelet therapy for patients with cerebrovascular disease.Methods According to the inclusion criteria, 153 patients with CYP2C19 (*2,*3,*17 ) gene detection were recruited between January 01, 2015 and April 1, 2017 in the First Affiliated Hospital of Kunming Medical University. Gene and genotype frequency of CYP2C19 (*2,*3,*17 ) were analyzed.All patients were divided into mutation group and non-mutation group according to the results of gene detection.The correlation between CYP2C19 gene point mutation and clinical data including characteristics of patients, ICVD and ischemic events after anti-platelet therapy were analyzed.Results In this study, there were 153 patients, including 70(45.8%) male and 83(54.2%) female patients, and the average age was (53.2 ±11.6 ) years.In this study, the frequency of genotype mutations in CYP2C19(*2,*3,*17) was 53.6%, 9.2%, and 2.0%respectively.The CYP2C19*2 mutations were correlated with smoking, alcohol consumption, cholesterol ( TC), and low density lipoprotein cholesterol(LDL-C) (P<0.05).CYP2C19*3 mutations were correlated with HDL-C(P<0.05).There was no correlation between the three gene locus mutations of CYP2C19 and ICVD ( P >0.05).The ischemic events after anti-platelet therapy were significantly increased in patients with CYP2C19*2 locus mutation(P<0.05).Conclusions The study draw the following conclusions through this clinical study. There is no significant correlation between the incidence of ICVD and the CYP 2C19(*2,*3 and*17) loci mutations.There is a statistically significance between CYP2C19*2 and ischemic events in patients with anti-platelet therapy.In this study, the mutation rate of CYP2C19*2 gene in 153 patients was as high as 53.6%.Therefore, patients should have genetic tests before receiving an anti-platelet therapy.It can reduce the possibility of poor prognosis for these patients.