本文選題：冠心病 + 氯吡格雷抵抗　； 參考：《蚌埠醫(yī)學院》2017年碩士論文

【摘要】：目的:探討血小板ADP受體P2Y12基因C34T和G52T位點是否突變與冠心病患者按規(guī)律服用氯吡格雷后是否產(chǎn)生氯吡格雷抵抗(CR)之間的相關性;評估CR對于行經(jīng)皮冠狀動脈支架植入術(PCI)的冠心病患者預后是否產(chǎn)生影響。方法:選取2015年1月至2015年12月在我院心內(nèi)科接受正規(guī)雙聯(lián)抗血小板治療并行PCI術的冠心病患者249例,采用基因芯片技術檢測患者血小板ADP受體P2Y12基因C34T和G52T兩個位點是否突變,并按突變與否對上述患者分組,根據(jù)結果分為C34T突變組(CT+TT型)/非突變組(CC型)、G52T突變組(GT+TT型)/非突變組(GG型)。隨后分別檢測每一位患者服用氯吡格雷前與規(guī)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%,就將其定為氯吡格雷抵抗。同時根據(jù)冠狀動脈造影結果統(tǒng)計每位患者冠狀動脈血管病變支數(shù)并做Gensini評分。最后經(jīng)過住院期間密切觀察,以及在上述患者出院后至少3個月間對其采用電話或門診的方式進行隨訪,統(tǒng)計患者預后情況。結果:249例患者中,男性155人,女性94人,平均年齡(64.8±11.1)歲。在C34T位點:CC型162例(65.1%),CT+TT型87例(34.9%),等位基因C頻率:73.9%,等位基因T頻率:26.1%,在G52T位點:GG型198例(79.5%),GT+TT型51例(20.5%),等位基因G頻率:85.5%,等位基因T頻率:14.5%�；�資料對比:G52T基因位點GT+TT組患者的年齡和男性比例要高于GG組,有統(tǒng)計學差異(P0.05);兩組患者吸煙、高血壓、糖尿病、生化常規(guī)指標等均無統(tǒng)計學差異(P0.05)。而C34T基因位點在年齡、性別等基線資料均無明顯差異(P值均0.05)。多因素Logistic回歸分析顯示,C34T位點CT+TT組CR發(fā)生率較CC組上升,為CR的獨立預測因子(OR:2.588,95%CI:1.4022~4.777,P0.01);對兩組觀察對象隨訪3個月至12個月,G52T位點GT+TT組較GG組PCI術后心血管事件發(fā)生率顯著提高(P0.05);各組冠脈病變支數(shù)和Gensini評分差異均無統(tǒng)計學意義。結論:P2Y12基因多態(tài)性(C34T與G52T)與急性冠脈綜合征患者氯吡格雷抵抗及冠脈介入術后的臨床預后密切相關。G52T基因位點突變會對冠心病PCI術患者的預后產(chǎn)生不良影響,使心血管事件發(fā)生率顯著提高,而C34T位點突變與否對患者預后沒有直接影響。P2Y12基因C34T位點突變是發(fā)生CR的獨立影響因素,表明C34T突變基因會對氯吡格雷的抗血小板聚集效果產(chǎn)生負面影響。
[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 鹵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.
【學位授予單位】：蚌埠醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.4

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