P2Y12基因多态性（C34T与G52T）与急性冠脉综合征患者氯吡格雷抵抗及冠脉介入术后临床预后的相关性研究

发布时间：2018-04-11 22:31

本文选题：冠心病 + 氯吡格雷抵抗　；参考：《蚌埠医学院》2017年硕士论文

【摘要】：目的:探讨血小板ADP受体P2Y12基因C34T和G52T位点是否突变与冠心病患者按规律服用氯吡格雷后是否产生氯吡格雷抵抗(CR)之间的相关性;评估CR对于行经皮冠状动脉支架植入术(PCI)的冠心病患者预后是否产生影响。方法:选取2015年1月至2015年12月在我院心内科接受正规双联抗血小板治疗并行PCI术的冠心病患者249例,采用基因芯片技术检测患者血小板ADP受体P2Y12基因C34T和G52T两个位点是否突变,并按突变与否对上述患者分组,根据结果分为C34T突变组(CT+TT型)/非突变组(CC型)、G52T突变组(GT+TT型)/非突变组(GG型)。随后分别检测每一位患者服用氯吡格雷前与规律服用一周后的血小板聚集率,如果服用氯吡格雷前后患者的血小板聚集率差值"f10%,就将其定为氯吡格雷抵抗。同时根据冠状动脉造影结果统计每位患者冠状动脉血管病变支数并做Gensini评分。最后经过住院期间密切观察,以及在上述患者出院后至少3个月间对其采用电话或门诊的方式进行随访,统计患者预后情况。结果:249例患者中,男性155人,女性94人,平均年龄(64.8±11.1)岁。在C34T位点:CC型162例(65.1%),CT+TT型87例(34.9%),等位基因C频率:73.9%,等位基因T频率:26.1%,在G52T位点:GG型198例(79.5%),GT+TT型51例(20.5%),等位基因G频率:85.5%,等位基因T频率:14.5%。基线资料对比:G52T基因位点GT+TT组患者的年龄和男性比例要高于GG组,有统计学差异(P0.05);两组患者吸烟、高血压、糖尿病、生化常规指标等均无统计学差异(P0.05)。而C34T基因位点在年龄、性别等基线资料均无明显差异(P值均0.05)。多因素Logistic回归分析显示,C34T位点CT+TT组CR发生率较CC组上升,为CR的独立预测因子(OR:2.588,95%CI:1.4022~4.777,P0.01);对两组观察对象随访3个月至12个月,G52T位点GT+TT组较GG组PCI术后心血管事件发生率显著提高(P0.05);各组冠脉病变支数和Gensini评分差异均无统计学意义。结论:P2Y12基因多态性(C34T与G52T)与急性冠脉综合征患者氯吡格雷抵抗及冠脉介入术后的临床预后密切相关。G52T基因位点突变会对冠心病PCI术患者的预后产生不良影响,使心血管事件发生率显著提高,而C34T位点突变与否对患者预后没有直接影响。P2Y12基因C34T位点突变是发生CR的独立影响因素,表明C34T突变基因会对氯吡格雷的抗血小板聚集效果产生负面影响。
[Abstract]:Objective: to investigate the relationship between C34T and G52T mutations of platelet ADP receptor P2Y12 gene and whether clopidogrel resistance was produced in patients with coronary heart disease after regular administration of clopidogrel.To assess whether CR affects the prognosis of patients with coronary heart disease undergoing percutaneous coronary stenting (PCI).Methods: from January 2015 to December 2015, 249 patients with coronary heart disease received regular dual antiplatelet therapy combined with PCI in our department of cardiology.The mutation of C34T and G52T of platelet ADP receptor P2Y12 gene was detected by gene chip technique, and the patients were divided into two groups according to the mutation or not.According to the results, the patients were divided into CT TT type / CC type G52T mutation group in C34T mutation group / GG type in non-mutation group.The platelet aggregation rates of each patient before and after taking clopidogrel for one week were then measured, and if the difference in platelet aggregation rate before and after clopidogrel was "f10, it was defined as clopidogrel resistance."At the same time, according to the results of coronary angiography, each patient coronary artery disease count and Gensini score.Finally, the patients were closely observed during hospitalization and followed up by telephone or outpatient service at least 3 months after discharge. The prognosis of the patients was counted.Results of 249 patients, 155 were male and 94 were female, with an average age of 64.8 卤11.1 years.The age and male ratio of patients with G52T gene locus GT TT was higher than that of GG group (P 0.05), and there was no significant difference in smoking, hypertension, diabetes, biochemical routine indexes between the two groups.However, there was no significant difference in age, sex and other baseline data of C34T gene locus (P < 0.05).Multivariate Logistic regression analysis showed that the CR rate in CT TT group was higher than that in CC group.As an independent predictor of CR, OR: 2.588C95 CI: 1.4022A4.777P0.01.The two groups were followed up for 3 months to 12 months. The incidence of cardiovascular events in GT group was significantly higher than that in GG group after PCI. There was no significant difference in the number of coronary lesion branches and Gensini score among the two groups.Conclusion the mutation of G52T gene locus associated with clopidogrel resistance in patients with acute coronary syndrome and clinical prognosis after coronary intervention may have a negative effect on the prognosis of PCI patients with coronary heart disease.The incidence of cardiovascular events was significantly increased, while C34T mutation had no direct effect on the prognosis of patients. P2Y12 gene C34T mutation was an independent influencing factor for CR.It was suggested that the C34T mutation gene had a negative effect on the antiplatelet aggregation of clopidogrel.
【学位授予单位】：蚌埠医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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