發(fā)布時(shí)間：2018-01-08 19:26

  本文關(guān)鍵詞：影響冠狀動(dòng)脈旁路移植術(shù)遠(yuǎn)期預(yù)后的基因多態(tài)性風(fēng)險(xiǎn)因素研究　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文　論文類(lèi)型：學(xué)位論文

  更多相關(guān)文章： 影響 冠狀動(dòng)脈 旁路 移植 遠(yuǎn)期 后的 基因 多態(tài)性 風(fēng)險(xiǎn) 因素 研究

【摘要】：冠狀動(dòng)脈旁路移植術(shù)(Coronary artery bypass grafting,CABG)是冠心病治療的主要手段之一,尤其是對(duì)于左主干病變、三支病變、合并糖尿病、左室功能不良等相對(duì)比較嚴(yán)重的冠心病患者。然而,.CABG患者遠(yuǎn)期出現(xiàn)死亡、心肌梗死、卒中及再次血運(yùn)重建等不良事件仍是困擾外科醫(yī)生及患者的主要難題。據(jù)報(bào)道,CABG術(shù)后5年內(nèi)發(fā)生主要不良心腦血管事件的比例達(dá)11.8%～31.0%,預(yù)測(cè)患者出現(xiàn)CABG術(shù)后遠(yuǎn)期不良心腦血管事件對(duì)于患者二級(jí)預(yù)防策略的優(yōu)化,提高患者遠(yuǎn)期預(yù)后具有重要意義。本研究對(duì)比了常用的臨床評(píng)分體系,評(píng)價(jià)了其在中國(guó)患者中預(yù)測(cè)遠(yuǎn)期不良事件的效能,發(fā)現(xiàn)目前常用的臨床評(píng)分體系對(duì)于我國(guó)冠心病搭橋患者遠(yuǎn)期不良事件的預(yù)測(cè)效果不甚理想,進(jìn)而建立了針對(duì)中國(guó)患者評(píng)價(jià)遠(yuǎn)期不良事件發(fā)生的基因風(fēng)險(xiǎn)模型,并對(duì)基因風(fēng)險(xiǎn)模型與臨床風(fēng)險(xiǎn)模型進(jìn)行了對(duì)比比較,將基因模型和臨床模型相結(jié)合,發(fā)現(xiàn)結(jié)合了臨床信息和基因信息的模型對(duì)于預(yù)測(cè)患者CABG術(shù)后遠(yuǎn)期不良事件的發(fā)生具有更高的應(yīng)用價(jià)值;進(jìn)而探索了基因多態(tài)性引起CABG術(shù)后遠(yuǎn)期不良事件發(fā)生的可能機(jī)制;最后針對(duì)特殊類(lèi)型的冠心病-左主干病變進(jìn)行了進(jìn)一步的研究,發(fā)現(xiàn)了與其發(fā)病相關(guān)的基因多態(tài)性同時(shí)與左主干患者行CABG后的不良事件發(fā)生具有關(guān)聯(lián)。第一部分 冠狀動(dòng)脈旁路移植術(shù)遠(yuǎn)期預(yù)后基因多態(tài)性風(fēng)險(xiǎn)評(píng)分的研究目的:評(píng)價(jià)現(xiàn)有主要的冠心病外科術(shù)后不良事件預(yù)測(cè)模型EuroSCORE、SinoSCORE和NYScore對(duì)于術(shù)后遠(yuǎn)期發(fā)生不良事件的預(yù)測(cè)價(jià)值;基于患者與術(shù)后遠(yuǎn)期發(fā)生不良事件相關(guān)的基因多態(tài)性,建立適用于我國(guó)CABG患者的風(fēng)險(xiǎn)評(píng)分體系,并對(duì)其進(jìn)行驗(yàn)證與評(píng)價(jià)。方法:本部分研究利用在阜外醫(yī)院行單純CABG手術(shù)的一組患者,利用生存分析的方法研究不同的臨床評(píng)分模型與術(shù)后遠(yuǎn)期不良事件發(fā)生之間的關(guān)聯(lián);通過(guò)C統(tǒng)計(jì)童和重分類(lèi)分析比較不同評(píng)分模型對(duì)于不同術(shù)后不良事件的預(yù)測(cè)價(jià)值。進(jìn)一步地,通過(guò)12個(gè)既往報(bào)道與冠心病患者不良事件發(fā)生相關(guān)的基因多態(tài)性位點(diǎn),利用生存分析探索其與CABG術(shù)后遠(yuǎn)期不良事件發(fā)生的關(guān)聯(lián),進(jìn)而采用其中與CABG術(shù)后不良事件發(fā)生相關(guān)的5個(gè)基因多態(tài)性位點(diǎn)建立預(yù)測(cè)患者CABG術(shù)后遠(yuǎn)期不良事件發(fā)生的基因風(fēng)險(xiǎn)評(píng)分體系,并對(duì)其做內(nèi)部驗(yàn)證。還通過(guò)C統(tǒng)計(jì)量、重分類(lèi)分析將其與臨床風(fēng)險(xiǎn)評(píng)分對(duì)比,探索基因風(fēng)險(xiǎn)評(píng)分聯(lián)合臨床風(fēng)險(xiǎn)評(píng)分對(duì)患者術(shù)后遠(yuǎn)期發(fā)生不良事件的預(yù)測(cè)效能。結(jié)果:三種評(píng)分中,EuroSCORE預(yù)測(cè)患者術(shù)后遠(yuǎn)期出現(xiàn)MACCE的HR為1.066(95%CI:1.001～1.136,p=0.048);SinoSCORE 預(yù)測(cè)患者術(shù)后遠(yuǎn)期出現(xiàn) MACCE 的 HR 為1.052(95%CI:1.016～1.088,p=0.004);NYScore 預(yù)測(cè)患者術(shù)后遠(yuǎn)期出現(xiàn) MACCE的HR為1.078(95%CI:1.032～1.126,p=0.001)。然而,三種基于臨床資料的評(píng)分體系對(duì)于預(yù)測(cè)術(shù)后發(fā)生MACCE的效能不高。在所有被研究的術(shù)后不良事件中,三種臨床評(píng)分體系對(duì)于術(shù)后全因死亡的預(yù)測(cè)效能最高。然而,三種評(píng)分模型對(duì)預(yù)測(cè)CABG術(shù)后遠(yuǎn)期MACCE的價(jià)值較小(AUC均0.60);三者在預(yù)測(cè)患者術(shù)后遠(yuǎn)期全因死亡方面的C統(tǒng)計(jì)量相對(duì)較大,分別為EuroSCORE 0.629(95%CI:0.574～0.684,p0.001);SinoSCORE0.629(95%CI:0.574～0.684,p0.001);NYScore0.646(95%CI:0.591～0.701,p0.001),說(shuō)明三種模型在預(yù)測(cè)全因死亡方面具有較好的區(qū)分度,預(yù)測(cè)效能好。SinoSCORE在預(yù)測(cè)CABG患者遠(yuǎn)期出現(xiàn)心肌梗死(C-index:0.613,95%CI:0.513～0.713,p=0.031)及再次血運(yùn)重建(C-index:0.601,95%CI:0.532～0.670,p=0.006)方面的效能較好。通過(guò)生存分析發(fā)現(xiàn)IL-6Rrs1800796(HR=1.268,95%CI:1.083～1.483,p=0.003),GPIArs 1126643(HR= 1.277,95%CI:1.081～1.508:,p=0.004),THBDrs1042579(HR=1.225,95%CI:1.031～1.455,p=0.021),P2RY12 rs2046934(HR=1.236,95%CI:1.022～1.494,p=0.029)和 CYP2C19 rs4244285(HR=1.185,95%CI:1.008～1.392,p=0.040)與術(shù)后遠(yuǎn)期MACCE的發(fā)生顯著相關(guān)�；�于這五個(gè)基因多態(tài)性位點(diǎn),建立針對(duì)CABG患者術(shù)后遠(yuǎn)期MACCE的風(fēng)險(xiǎn)評(píng)分體系,發(fā)現(xiàn)該評(píng)分對(duì)于患者發(fā)生遠(yuǎn)期MACCE的風(fēng)險(xiǎn)預(yù)測(cè)能力高于臨床風(fēng)險(xiǎn)評(píng)分;通過(guò)C統(tǒng)計(jì)量、Hosmer-Lemeshow統(tǒng)計(jì)量與重分類(lèi)分析研究發(fā)現(xiàn),同時(shí)利用基因風(fēng)險(xiǎn)評(píng)分與臨床風(fēng)險(xiǎn)評(píng)分評(píng)價(jià)患者術(shù)后MACCE的發(fā)生,其效能達(dá)到最佳。結(jié)論:相較而言,三種臨床評(píng)分體系對(duì)于預(yù)測(cè)患者遠(yuǎn)期出現(xiàn)MACCE事件的能力并不強(qiáng),需要對(duì)此內(nèi)容的進(jìn)一步研究以明確預(yù)測(cè)中國(guó)患者遠(yuǎn)期出現(xiàn)MACCE的模型,或加入其他關(guān)鍵變量提高對(duì)中國(guó)患者遠(yuǎn)期不良事件發(fā)生的預(yù)測(cè)能力。針對(duì)患者CABG術(shù)后遠(yuǎn)期風(fēng)險(xiǎn)的基因風(fēng)險(xiǎn)評(píng)分體系對(duì)于預(yù)測(cè)國(guó)人CABG術(shù)后MACCE發(fā)生的效能優(yōu)于臨床風(fēng)險(xiǎn)評(píng)分;同時(shí)應(yīng)用臨床風(fēng)險(xiǎn)評(píng)分和基因風(fēng)險(xiǎn)評(píng)分的預(yù)測(cè)效能最高。研究說(shuō)明,基因風(fēng)險(xiǎn)評(píng)分能夠提高對(duì)患者遠(yuǎn)期發(fā)生MACCE的預(yù)測(cè)能力,對(duì)于CABG術(shù)后患者的二級(jí)預(yù)防策略?xún)?yōu)化及防止不良事件發(fā)生具有重要意義。第二部分血小板膜糖蛋白GPIA的基因多態(tài)性對(duì)于冠狀動(dòng)脈旁路移植術(shù)后遠(yuǎn)期不良事件的作用及機(jī)制研究目的:2驗(yàn)證并研究GPIArs1126643位點(diǎn)對(duì)于CABG術(shù)后遠(yuǎn)期不良事件發(fā)生的作用和機(jī)制。方法:本部分研究通過(guò)發(fā)現(xiàn)隊(duì)列和驗(yàn)證隊(duì)列證實(shí)了 GPIArs1126643基因多態(tài)性T等位基因與CABG術(shù)后遠(yuǎn)期不良事件發(fā)生的關(guān)聯(lián);并通過(guò)另一組功能研究隊(duì)列,對(duì)血小板聚集實(shí)驗(yàn)進(jìn)一步研究了該基因多態(tài)性對(duì)于血小板聚集的影響,進(jìn)而通過(guò)qRT-PCR和Western-blotting實(shí)驗(yàn)探索了該基因多態(tài)性引起患者CABG術(shù)后遠(yuǎn)期不良事件發(fā)生的可能機(jī)制。結(jié)果:發(fā)現(xiàn)隊(duì)列中GPIArs1126643 T等位基因攜帶者發(fā)生MACCE的風(fēng)險(xiǎn)是CC純合患者的1.27倍(p=0.033);在驗(yàn)證隊(duì)列中,其多態(tài)性T等位基因攜帶者發(fā)生MACCE的風(fēng)險(xiǎn)是CC純合型患者的1.74倍(p=0.020)。在功能研究對(duì)列中,T等位基因攜帶者血小板最大聚集率的平均值為68.3%,顯著高于CC純合型患者的58.8%(p=0.029),通過(guò)qRT-PCR實(shí)驗(yàn),我們發(fā)現(xiàn)GPIArs1126643 T等位基因攜帶者的GPIAmRNA水平與CC純合型患者無(wú)明顯差異,而其多態(tài)性T等位基因攜帶者GpIa蛋白表達(dá)是CC純合型患者的2.08倍,具有顯著的統(tǒng)計(jì)學(xué)意義(p0.001)。結(jié)論:GPIArs1126643通過(guò)轉(zhuǎn)錄后調(diào)控影響患者GpIa蛋白質(zhì)的表達(dá),進(jìn)而影響其血小板聚集率:T等位基因攜帶者的平均血小板聚集率更高。由此,GPIArs1126643T等位基因攜帶者CABG術(shù)后遠(yuǎn)期發(fā)生不良事件的可能性更高。第三部分環(huán)氧化酶COX-2基因多態(tài)性與冠心病左主干病變及其預(yù)后的研究目的:研究環(huán)氧化酶COX-2基因多態(tài)性與冠心病左主干病變的發(fā)生是否有關(guān)聯(lián),并研究這種關(guān)聯(lián)是否影響患者行CABG術(shù)遠(yuǎn)期的預(yù)后。方法:本部分研究在一組阜外醫(yī)院行CABG手術(shù)的患者中,探索了三個(gè)位于COX-2基因的基因多態(tài)性rs5275、rs689466和rs5277與冠心病左主干疾病發(fā)生之間的關(guān)聯(lián),并通過(guò)生存分析研究了其與患者行CABG手術(shù)遠(yuǎn)期預(yù)后的關(guān)聯(lián)。結(jié)果:研究發(fā)現(xiàn)rs5275與rs689466都不增加冠脈左主干的發(fā)生風(fēng)險(xiǎn)(rs5275:單因素分析:OR=1.00,p=0.998;校正后:OR=1.00,p=0.994。rs689644:單因素分析:OR=1.08,p=0.577;校正后:OR=1.590,p=0.013)。而對(duì)于 rs5277 位點(diǎn),其 C 等位基因攜帶者出現(xiàn)左主干病變的可能性為GG純合型患者的1.58倍,95%置信區(qū)間為1.10～2.26,p=0.014,有顯著的統(tǒng)計(jì)學(xué)意義。在經(jīng)過(guò)多因素的校正后,C等位基因攜帶者出現(xiàn)左主干病變的可能性仍為GG純合型患者的1.59倍,95%置信區(qū)間為1.10～2.29,p=0.013,具有顯著的統(tǒng)計(jì)學(xué)意義。另外,rs5277C等位基因攜帶者發(fā)生MACCE的風(fēng)險(xiǎn)是GG純合型患者的1.56倍(p=0.037),經(jīng)過(guò)多因素校正后其風(fēng)險(xiǎn)仍是GG純合型患者的1.56倍(p=0.038)。對(duì)于左主干病變患者,rs5277C等位基因攜帶者發(fā)生MACCE的風(fēng)險(xiǎn)是GG純合型患者的2.04倍(p=0.033),經(jīng)過(guò)多因素校正后其風(fēng)險(xiǎn)仍是GG純合型患者的2.01倍(p=0.039);而在非左主干患者中,rs5277基因多態(tài)性則與CABG術(shù)后遠(yuǎn)期MACCE沒(méi)有相關(guān)性(單因素生存分析p=0.273;多因素生存分析p=0.259)。結(jié)論:本部分研究通過(guò)環(huán)氧化酶COX-2的3個(gè)基因多態(tài)性位點(diǎn)與冠狀動(dòng)脈左主干疾病的關(guān)聯(lián)性研究,發(fā)現(xiàn)COX-2 rs5277 C等位基因能夠增加左主干疾病的發(fā)生風(fēng)險(xiǎn),進(jìn)一步的研究發(fā)現(xiàn)該等位基因增加冠心病左主干病變患者,行冠狀動(dòng)脈旁路移植術(shù)術(shù)后的遠(yuǎn)期主要不良心腦血管事件的發(fā)生風(fēng)險(xiǎn),而不影響非左主干患者的預(yù)后。該部分研究的結(jié)論提示,對(duì)于COX-2rs5277C等位基因攜帶者,需要較多關(guān)注其左主干的病變狀況,對(duì)于具有該等位基因的左主干疾病患者,應(yīng)當(dāng)給予強(qiáng)化的抗炎等相關(guān)治療,以期提高患者預(yù)后。
[Abstract]:Coronary artery bypass grafting (Coronary artery bypass grafting, CABG) is one of the main means of treatment of coronary heart disease, especially for the left main coronary artery disease, diabetes mellitus and three lesions, and left ventricular dysfunction in patients with coronary heart disease is relatively serious. However, the long-term.CABG patients died of myocardial infarction, the main problem for surgeons and patients is still troubled by the stroke and revascularization and other adverse events. According to reports, occurrence of major adverse cardiovascular events within 5 years after CABG the proportion of 11.8% to 31%, forecast CABG patients postoperative long term cardiovascular events for patients with optimization of two grade prevention strategy, has important significance in improving the prognosis of the patients. This study compared the clinical scoring system used, evaluate its effectiveness in predicting long-term adverse events Chinese patients, found that the current commonly used clinical scoring system for The prediction effect of Chinese coronary artery bypass patients with long-term adverse events is not ideal, and set up the risk model for gene China patients evaluated the long-term adverse events, and the genetic risk model and clinical risk model have been compared, combined with the genetic model and clinical model, found a combination of clinical information and genetic information model the prediction has higher application value in patients with CABG long-term postoperative adverse events; and to explore the possible mechanism of CABG gene polymorphism caused by long-term postoperative adverse events; according to the special type of coronary heart disease - makes a further study of left main disease, found the gene polymorphism and pathogenesis related with adverse the event left main patients after CABG occurred. The first part is associated with coronary artery bypass graft prognosis gene polymorphism of wind Objective: To evaluate the risk score of major coronary surgery postoperative adverse events prediction model of EuroSCORE, SinoSCORE and NYScore in prediction of adverse events and long-term postoperative adverse events; gene polymorphism related to the long-term prognosis of patients with postoperative based on building suitable for Chinese CABG patients and the risk score system. Verification and evaluation on it. Methods: in a group of patients underwent CABG surgery in Fuwai Hospital using this part of the study, research and clinical scoring model operation after different long-term adverse events associated with hair between students by using the method of survival analysis; through C statistical children and re classification analysis and comparison of different scoring models to predict the value of different postoperative adverse events. Further, by 12 previous reports of adverse events in patients with coronary heart disease related gene polymorphism, using survival analysis to explore the Associated with the long-term incidence of adverse events after CABG, then the one with the CABG was established to predict the occurrence of long-term adverse events in patients with postoperative CABG risk score system associated gene 5 gene polymorphism after adverse events, and internal verification on it. Through the C statistics, analysis of the classification score with the comparison of clinical risk, explore genetic risk score combined with clinical risk score in the prediction of adverse events on the long-term efficacy of patients after surgery. Results: three scores, EuroSCORE predict postoperative long-term MACCE HR 1.066 (95%CI: 1.001 ~ 1.136, p=0.048); SinoSCORE predict postoperative long-term MACCE HR 1.052 (95%CI:1.016 - 1.088, p=0.004); NYScore predict postoperative long-term MACCE HR 1.078 (95%CI:1.032 - 1.126, p=0.001). However, the clinical data of three score system based on MACCE predicting postoperative effectiveness is not high. In all of the postoperative adverse events, three clinical scoring system for postoperative all-cause death of the highest prediction efficiency. However, the three score model for the value of small forward MACCE prediction after CABG (AUC < 0.60); three in the prediction of patients long term postoperative death from all aspects of the C statistic is relatively large, respectively 0.629 EuroSCORE (95%CI:0.574 - 0.684, p0.001); SinoSCORE0.629 (95%CI:0.574 - 0.684, p0.001); NYScore0.646 (95%CI:0.591 - 0.701, p0.001), shows three kinds of model test of all-cause death has good discrimination in the pre forecast performance of.SinoSCORE myocardial infarction in patients with long-term prediction CABG (C-index:0.613,95%CI:0.513 - 0.713, p=0.031) and revascularization (C-index:0.601,95%CI:0.532 - 0.670, p=0.006) the effect is good. The survival analysis showed that IL-6Rrs18 00796 (HR=1.268,95%CI:1.083 - 1.483, p=0.003), GPIArs 1126643 (HR= 1.277,95%CI:1.081 ~ 1.508:, p=0.004), THBDrs1042579 (HR=1.225,95%CI:1.031 - 1.455, p=0.021), P2RY12 rs2046934 (HR=1.236,95%CI:1.022 - 1.494, p=0.029) and CYP2C19 rs4244285 (HR=1.185,95%CI:1.008 - 1.392, p=0.040) was significantly associated with the occurrence of postoperative long-term MACCE sites of these five genes. Based on the established risk score for polymorphism, system long term MACCE CABG after surgery, found that the risk of patients with MACCE score for long-term prediction ability is higher than the clinical risk score; through C statistic, Hosmer-Lemeshow statistic and analysis of classification with gene risk score and clinical risk score evaluation of patients after MACCE, the to achieve the best performance. Conclusion: in contrast, three clinical scoring system for predicting long-term MAC patients CE event is not strong, needs further study of the content to determine predictive Chinese patients with long-term MACCE model, or the addition of other key variables to improve the ability to predict the occurrence of adverse events in patients with long-term Chinese. According to the long-term risk of wind gene in patients with CABG after risk scoring system for the prediction of Chinese CABG postoperative MACCE clinical risk the score is better than forecast performance; at the same time the application of clinical risk score and genetic risk score highest. Research shows that genetic risk score can improve the prediction ability of MACCE occurred in patients with long term, has important significance for patients after CABG two grade prevention strategy optimization and prevent adverse events. The second part gene polymorphism of platelet objective to study the membrane glycoprotein GPIA for coronary artery bypass graft long-term postoperative adverse events: the effect and mechanism of 2 verification and study G PIArs1126643 site for the effects and mechanisms of long-term adverse events after CABG. Methods: This study found that by cohort and a validation cohort confirmed the association of long-term adverse events GPIArs1126643 gene polymorphism of T allele and CABG after operation; and by another group to study cohort, further study of the gene polymorphism the effect of platelet aggregation experiments on platelet, and then through the qRT-PCR and Western-blotting experiments explored the possible mechanisms of long-term adverse events in patients with CABG after the gene polymorphism. Results: it was found that the risk of GPIArs1126643 T in a cohort of allele MACCE was 1.27 times CC homozygous patients (p=0.033) in the verification; in the queue, the risk of the polymorphism of T allele of MACCE was 1.74 times in patients with CC homozygous (p=0.020). To study the function of the column, T etc. The average value of gene carriers the maximum platelet aggregation rate was 68.3%, significantly higher than that of CC homozygous patients 58.8% (p=0.029), through qRT-PCR test, we found no significant difference between GPIAmRNA levels and CC GPIArs1126643 T allele homozygous, and the polymorphism of T allele of GpIa protein expression is 2.08 times in patients with homozygous CC, with significant statistical significance (p0.001). Conclusion: GPIArs1126643 can influence the regulation of the expression of GpIa protein in patients after transcription, thereby affecting the platelet aggregation rate of platelet T: the average allele aggregation rate higher. Thus, the long-term GPIArs1126643T allele carriers after CABG possibility adverse events more. Objective: third part of cyclooxygenase COX-2 gene polymorphism and coronary heart disease left main disease and prognosis: a study of cyclooxygenase COX-2 gene polymorphism Left main lesion and the occurrence of coronary heart disease is related, and to study whether this association affects the prognosis of CABG patients long-term. Methods: this part of the study in a group of patients underwent CABG surgery in Fuwai Hospital, explores three located in the COX-2 gene rs5275 polymorphism and the association between rs689466 and rs5277 and left main coronary heart disease the occurrence of disease, and through the analysis on the survival associated with the long-term prognosis of patients underwent CABG surgery. Results: the study found that rs5275 and rs689466 did not increase the risk of left main coronary rs5275: (single factor analysis: OR =1.00, p=0.998; OR=1.00, p=0.994.rs689644:: after correction of single factor analysis: OR=1.08, p=0.577; correction: OR=1.590, p=0.013). For the rs5277 locus, the C allele possibility of left main disease 1.58 times for patients with homozygous GG, 95% confidence interval was 1.10 ~ 2.26, p= 0.014, there was statistical significance. After adjustment for multiple factors, C allele possibility of left main coronary artery disease is still 1.59 times in patients with homozygous GG, 95% confidence interval was 1.10 ~ 2.29 p=0.013, with significant statistical significance. In addition, the risk rs5277C allele MACCE the 1.56 times in patients with GG homozygous (p=0.037), after multivariable adjustment after the risk is 1.56 times the GG homozygous patients (p=0.038). For patients with left main disease, the risk of rs5277C allele of MACCE was 2.04 times in patients with GG homozygous (p=0.033), after the adjusted risk is 2.01 times the GG homozygous patients (p=0.039); while in non left main patients, rs5277 gene polymorphism is not associated with long-term postoperative MACCE (CABG multi factor analysis p=0.273; univariate survival analysis p=0.259). Conclusion: the Association of research through the cyclooxygenase 3 COX-2 gene polymorphism and left main coronary artery disease, found that the COX-2 rs5277 C allele could increase the risk of left main disease, further research found that the allele increased in patients with coronary heart disease and left main disease, the risk of coronary artery bypass grafting after the long-term major adverse cardiovascular events, but does not affect the prognosis of patients with non left trunk. This part of research conclusion, the COX-2rs5277C allele carriers, need to pay more attention to the status of left main lesions, with the alleles of the left main coronary artery disease patients, should be given to strengthen anti-inflammatory and other related treatment and in order to improve the prognosis of the patients.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R654.2

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