本文關鍵詞：CYP2B6，B4GALT2基因多態(tài)性及生化學因素對冠心病患者氯吡格雷抗血小板作用的影響　出處：《安徽醫(yī)科大學》2017年碩士論文　論文類型：學位論文

  更多相關文章： 冠心病 CR MACE 遺傳因素 生化學因素

【摘要】：目的:探討CYP2C19、CYP1A2、B4GALT2、VEGFR-2、PEAR1、IRS-1、CYP2B6、PON1基因多態(tài)性對氯吡格雷抗血小板作用的影響。探討生化學因素對氯吡格雷抗血小板作用的影響及可能的作用機制。方法:納入自2014年6月到2016年9月在安徽省某兩家大型三甲醫(yī)院行CAG手術的冠心病患者,所有患者術前均接受雙重抗血小板治療(口服氯吡格雷負荷劑量300mg+維持劑量75mg/d,口服阿司匹林負荷劑量100mg+維持劑量100mg/d,接受PCI手術的患者術后繼續(xù)服用氯吡格雷至少12個月)。術后第二天晨起空腹靜脈采血4m L。1.所有患者均測定最大血小板聚集率(MAR),通過電阻抗法。2.采用Sequenom Mass Array系統(tǒng)進行CYP2C19、CYP1A2、B4GALT2、VEGFR-2、PEAR1、IRS-1、CYP2B6、PON1基因分型。3.通過住院病歷收集患者的血常規(guī),肝腎功能等生化學指標。4.通過病程記錄、門診或電話隨訪PCI患者患者術后一年內MACE的發(fā)生情況,主要心血管事件(MACE)包括心絞痛再發(fā)(RA)、支架血栓(ST),心肌梗死(MI),靶病變血運重建(TVR),卒中(Stroke),及心源性死亡(CD)。5.運用Matlab 2012a統(tǒng)計軟件和Haploview 4.2遺傳分析軟件研究遺傳因素,生化學因素與氯吡格雷療效的關聯(lián)。結果:1.本研究共納入283名患者,接受CAG并PCI手術的患者172例,僅行CAG手術的患者111例,其中發(fā)生MACE的患者有34例。MAR:正常組vs MACE組MAR(42.51±12.59)%vs(50.07±13.08)%,P0.05;2.分析等位基因與MAR和MACE的關聯(lián):顯性基因模型下不同基因型患者MAR比較:CYP2B6 rs2279343 AA vs GG+AG,(42.9±12.6)%vs(45.5±11.7)%,P=0.045,B4GALT2 rs1061781 CC vs TT+CT,(44.6±12.2)%vs(41.7±12.4)%,P=0.048,差異具有統(tǒng)計學意義。顯性基因模型下不同基因型患者MACE發(fā)生率比較:CYP2B6 rs2279343 AA vs GG+AG,0.087 vs 0.156,P=0.039,差異具有統(tǒng)計學意義。以上結果提示,CYP2B6 rs2279343位點與血小板聚集率,MACE顯著相關,B4GALT2 rs1061781位點與血小板聚集率顯著相關。其他位點的遺傳變異與MAR,MACE均無顯著相關性。3.分析生化學參數(shù)與MAR和MACE的關聯(lián):生化學參數(shù)HGB,RDW-CV在CR組和非CR組比較:HGB在CR組vs非CR組,(130.18±17.34)vs(118.88±25.16),P=0.0006,RDW-CV在CR組vs非CR組,(13.56±1.32)vs(14.31±1.67),P=0.0017,MCV在MACE組與非MACE組,(91.94±6.03)vs(87.34±21.36)P=0.0456,差異有統(tǒng)計學意義,且變化趨勢與貧血相一致,提示貧血可能影響冠心病患者氯吡格雷療效。結論:1.CYP2B6 rs2279343、B4GALT2 rs1061781基因多態(tài)性與氯吡格雷臨床療效具有相關性。2.生化學參數(shù)HGB,RDW-CV和MCV影響氯吡格雷的抗血小板作用,提示貧血可能對氯吡格雷的療效有影響。3.PEAR1 rs12041331 GA,rs41273215 CT、CYP1A2 rs2069514 GA,rs762551CA、IRS1 rs13431554 AG、CYP3A4 rs2242480 CT、VEGFR-2 rs2305948 CT、CYP2B6 rs8192709 CT,、PON1 rs662 TC,rs854560 AT與氯吡格雷臨床療效均無顯著相關性。
[Abstract]:Objective: To investigate the CYP2C19, CYP1A2, B4GALT2, VEGFR-2, PEAR1, IRS-1, CYP2B6, PON1 gene polymorphism on the antiplatelet effect of clopidogrel. To investigate the effects of chemical factors on the antiplatelet effect of clopidogrel and its possible mechanism. Methods: patients from June 2014 to September 2016 in Anhui province two large hospital underwent CAG surgery for coronary heart disease patients, all patients received dual antiplatelet therapy (oral clopidogrel loading dose 300mg+ dose 75mg/d, oral aspirin loading dose 100mg+ dose of 100mg/d, patients undergoing PCI surgery after surgery to take clopidogrel at least 12 months). After second days of fasting venous blood of all patients were measured 4m L.1. maximum platelet aggregation rate (MAR), the resistance method using Sequenom Array system.2. Mass CYP2C19, CYP1A2, B4GALT2, VEGFR-2, PEAR1, IRS-1, CYP2B6, PON1 genotyping by.3. medical records were collected blood, liver and kidney function and other biochemical indexes by.4. records, a year of outpatient or telephone follow-up occurred in PCI patients after surgery in the MACE case, major cardiovascular events (MACE) including recurrent angina pectoris (RA), stent thrombosis (ST), myocardial infarction (MI), target lesion revascularization (TVR), stroke (Stroke), and cardiac death (CD) using.5. Matlab 2012a statistical software and Haploview 4.2 genetic analysis software to study the genetic factors, biochemical factors associated with halosulfuron Gray effect. Results: 1. were included in the study 283 patients, 172 patients underwent CAG and PCI surgery, 111 patients only underwent CAG surgery, which occurs in MACE of patients with 34 cases of normal.MAR: group vs MACE group MAR (42.51 + 12.59)%vs (50.07 + 13.08)%, P0.05; correlation analysis of 2. alleles with MAR and MACE the dominant gene model Comparison of different genotypes in MAR: CYP2B6 rs2279343 AA vs GG+AG, (42.9 + 12.6)%vs (45.5 + 11.7)%, P=0.045, B4GALT2 rs1061781 CC vs TT+CT, (44.6 + 12.2)%vs (41.7 + 12.4)%, P=0.048, the difference was statistically significant. The dominant gene model under different genotype patients the incidence of MACE CYP2B6 rs2279343 AA vs GG+AG: 0.087, vs 0.156, P=0.039, the difference was statistically significant. These results suggest that CYP2B6 rs2279343 polymorphism with platelet aggregation was significantly related to MACE, B4GALT2, rs1061781 loci and platelet aggregation was significantly correlated. Genetic variation and other MAR sites, MACE was no significant correlation between.3. analysis biochemical parameters associated with MAR and MACE: biochemical parameters of HGB, RDW-CV in CR group and non CR group: HGB group CR vs in non CR group, (130.18 + 17.34) vs (118.88 + 25.16), P=0.0006, RDW-CV in CR group vs CR group, (13.56 + 1.32 (VS) 14.31 + 1.67), P=0.0017, MCV in MACE group and non MACE group, (91.94 + 6.03) vs (87.34 + 21.36) P=0.0456, the difference was statistically significant, and the change trend is consistent with anemia, suggesting that anemia may affect the efficacy of clopidogrel in patients with coronary heart disease. Conclusion: 1.CYP2B6 rs2279343, B4GALT2 rs1061781 gene polymorphism and clinical efficacy of clopidogrel associated with biochemical.2. the parameters HGB, RDW-CV and MCV affected the antiplatelet effect of clopidogrel, suggesting that anemia may have effects of.3.PEAR1 rs12041331 GA, rs41273215 CT effect of clopidogrel, CYP1A2 rs2069514 GA, rs762551CA IRS1, rs13431554 AG, CYP3A4 rs2242480 CT, VEGFR-2 rs2305948 CT, CYP2B6 rs8192709 CT, PON1 rs662, TC, rs854560 and AT had no clinical curative effect of clopidogrel significant correlation.

【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.4

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