细胞色素P450 2C19 G681A基因多态性与北方汉族冠心病患者氯吡格雷抵抗的关系探讨

目的 探讨细胞色素P450 2C19（CYP2C19） G681A基因多态性与氯吡格雷抵抗（CR）的关系,以期早期筛选和识别CR.方法 共纳入对象136例,其中73例为急性冠状动脉综合征（ACS）患者,63例为稳定性心绞痛（SAP）患者.对所有入选对象进行血管舒张剂刺激磷酸蛋白（VASP）磷酸化程度的检测,按照测得的VASP磷酸化指数（VASP index）将患者分为CR组和NCR组,CR定义为VASP index≥50％.采用聚合酶链反应-限制性片段长度多态性技术联合双脱氧sanger测序法,检测所有患者的基因型,分析各基因型和等位基因在两组之间的分布.结果 入选人群CR发生率为58.8％（80例）,ACS患者的CR发生率高于SAP患者（67.1％vs.49.2％,P＜0.05）.CYP2C19基因G681A多态性位点三种基因型（CG、GA、AA）在CR组与NCR组的分布频率分别为47.54％,46.22％,6.24％和69.63％,26.80％,3.57％,在两组间,三种基因型的分布存在差异（P＜0.05）.A等位基因的频率在CR组高于NCR组（29.37％vs.16.96％,P＜0.05）,A等位基因增加CR的发生风险（OR =2.04,95％ CI：1.12～ 3.71,P＜0.05）.Logistic回归校正了性别、年龄、体重指数、高血压病、2型糖尿病等因素后,发现CYP2C19基因G681A单核苷酸多态性仍与CR的发生风险有关（OR =3.259,95％ CI：1.476～6.764,P＜0.001）.结论 细胞色素P450 2C19 G681A基因多态性和CR的发生相关,A等位基因可能是导致CR发生的重要遗传学因素.

Association between CYP2C19 G681A gene polymorphisms and clopidogrel resistance in the Han population of North China with coronary atherosclerotic heart disease

Objective To elucidate the preliminary association between Cytochrom P450 2C19（CYP2C19） gene G681 A polymorphisms and CR in the Han population of North China with coronary artery disease （CAD）. Methods A total of 136 patients （73 with acute coronary sydrome and 60 with stable angian pectoris）were enrolled. The vasodilator-stimulated phosphoprotein （VASP） phosphorylation state was determined in all patients received a 600 mg loading dose of Clopidogrel. Patients enrolled were divided into CR group and Non-CR group according to the value of VASP index. VASP index of≥50% was regarded as CR. The presence of CYP2C19G681A polymorphisms was determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis combined with sanger dideoxy mediated chain termination method. Then the distribution of the frequencies of genotypes and alleles among CR and NCR groups was analyzed. Results There were 80 patients in the CR group, indicating the occurrence of CR at a rate of 58.82%. Compared with SAP,patients with ACS were at a higher rate of occurrence of CR（67. 1% vs. 49. 2% ,P 〈 0.05 ）. The genotype（GG/GA/AA） distribution of the CYP2C19 G681A gene polymorphisms were 47.54% ,46. 22% ,6. 24% and 69. 63% ,26. 80% ,3.57% in the CR and NCR groups, respectively. Statistically significant difference was observed between CR and NCR groups for distribution of the genotypes（P 〈 0. 05）. Frequency of A allele was significantly higher in CR group than in NCR group（29.37% vs. 16. 96% ,P 〈 0. 05）, A allele carriers were more likely to develop C R（ OR = 2. 04,95% CI：I. 12-3.71,P 〈 0. 05 ）.Logistic regression analysis adjusted for the presence of traditional risk factors including age, gender, BMI, hypertention,type2 diabetes, the CYP2C19G681A polymorphism resulted an independent risk factor for CR （OR = 3. 259,95% CI：I. 476-6. 764,P 〈0. 001 ）＇. Conclusion CyP2C19 gene G681A single nucleotide polymorphism is associated with the occurrence of CR;A allele might be an important genetic risk factor for the development of CR.