青海地区汉族冠心病患者氯吡格雷代谢关键酶CYP2C19基因多态性分析

Genetic polymorphism analysis of CYP2C19 in Han Chinese patients with coronary heart disease in Qinghai area

目的通过分析青海地区汉族冠心病患者氯吡格雷代谢关键酶CYP2C19基因多态性,为临床抗血小板药物的个体化精准治疗提供参考。方法选取青海地区汉族冠心病患者403例,采集患者静脉血,实时荧光定量PCR法分析CYP2C19基因序列,根据PCR结果判定CYP2C19基因型及代谢表型,Hardy-weinberg平衡检验分析数据的群体代表性,比较相关文献中不同地区间CYP2C19代谢表型。结果403例汉族CHD患者CYP2C19*1、CYP2C19*2、CYP2C19*3、CYP2C19*17等位基因频率分别为60.55%、30.77%、5.70%、2.98%;CYP2C19*1/*1、CYP2C19*1/*2、CYP2C19*1/*3、CYP2C19*2/*2、CYP2C19*2/*3、CYP2C19*3/*3、CYP2C19*1/*17、CYP2C19*2/*17、CYP2C19*3/*17、CYP2C19*17/*17基因型频率分别为40.2%、30.8%、6.7%、12.2%、4.0%、0.2%、3.2%、2.5%、0.2%。Hardy-Weinberg平衡检验显示,青海地区汉族CHD患者CYP2C19基因型频率符合Hardy-Weinberg平衡,具有良好的群体代表性。CYP2C19代谢表型超快代谢型、快代谢型、中间代谢型及慢代谢型分别为13例(3.20%)、162例(40.2%)、162例(40.2%)及66例(16.4%)。青海地区汉族CHD患者与北京、甘肃、宁夏、陕西、广州地区汉族CHD患者CYP2C19代谢表型比较,差异均有统计学意义(P均<0.05)。结论青海地区汉族CHD患者基因型以CYP2C19*1/*1、CYP2C19*1/*2为主。与国内其他地区比较,青海地区CHD患者存在氯吡格雷抵抗的风险较高。

Objective By analyzing the gene polymorphisms of CYP2C19,a key enzyme for clopidogrel metabo⁃lism,in Han Chinese patients with coronary heart disease(CHD)in Qinghai region,in order to provide a reference for the individualized and precise treatment of clinical antiplatelet drugs.Methods We selected 403 cases of Han Chinese pa⁃tients with CHD in Qinghai region,collected patients'venous blood,and analyzed CYP2C19 gene sequences by real-time fluorescence quantitative PCR.According to the PCR results,we determined CYP2C19 genotypes and metabolic pheno⁃types.Hardy-Weinberg equilibrium test was used to analyze the data's group representativeness,and we compared the metabolic phenotypes of CYP2C19 among different regions in the relevant literature.Results The allele frequencies of CYP2C19*1,CYP2C19*2,CYP2C19*3,and CYP2C19*17 in 403 Han Chinese CHD patients were 60.55%,30.77%,5.70%,and 2.98%,respectively.And the frequencies of CYP2C19*1/*1,*1/*2,*1/*3,*2/*2,*2/*3,*3/*3,*1/*17,*2/*17,*3/*17 genotypes were 40.2%,30.8%,6.7%,12.2%,4.0%,0.2%,3.2%,2.5%,and 0.2%,re⁃spectively.The Hardy-Weinberg equilibrium test showed that the CYP2C19 genotype frequencies of Han Chinese CHD pa⁃tients in Qinghai were in accordance with the Hardy-weinberg equilibrium(P<0.05),with a good representation of the group.The frequencies of different metabolic phenotype in the patients were as follows:13 cases of ultra fast metabolizer(3.20%),162 cases of extensive metabolizer(40.2%),162 cases of intermediate metabolizer(40.2%)and 66 cases of poor metabolizer(16.4%).There were significant differences in the distribution of metabolic phenotypes between Han Chinese CHD patients in Qinghai area and Han Chinese CHD patients in Beijing,Gansu,Ningxia,Shanxi and Guangzhou areas(all P<0.05).Conclusions The genotypes of Han Chinese CHD patients in Qinghai region were dominated by CYP2C19*1/*1 and CYP2C19*1/*2.Compared with other regions in China,the risk of clopidogrel resistance was higher in CHD patients in Qinghai region.