CYP2B6，B4GALT2基因多态性及生化学因素对冠心病患者氯吡格雷抗血小板作用的影响

发布时间：2018-01-12 17:11

本文关键词：CYP2B6，B4GALT2基因多态性及生化学因素对冠心病患者氯吡格雷抗血小板作用的影响　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

更多相关文章： 冠心病 CR MACE 遗传因素 生化学因素

【摘要】：目的:探讨CYP2C19、CYP1A2、B4GALT2、VEGFR-2、PEAR1、IRS-1、CYP2B6、PON1基因多态性对氯吡格雷抗血小板作用的影响。探讨生化学因素对氯吡格雷抗血小板作用的影响及可能的作用机制。方法:纳入自2014年6月到2016年9月在安徽省某两家大型三甲医院行CAG手术的冠心病患者,所有患者术前均接受双重抗血小板治疗(口服氯吡格雷负荷剂量300mg+维持剂量75mg/d,口服阿司匹林负荷剂量100mg+维持剂量100mg/d,接受PCI手术的患者术后继续服用氯吡格雷至少12个月)。术后第二天晨起空腹静脉采血4m L。1.所有患者均测定最大血小板聚集率(MAR),通过电阻抗法。2.采用Sequenom Mass Array系统进行CYP2C19、CYP1A2、B4GALT2、VEGFR-2、PEAR1、IRS-1、CYP2B6、PON1基因分型。3.通过住院病历收集患者的血常规,肝肾功能等生化学指标。4.通过病程记录、门诊或电话随访PCI患者患者术后一年内MACE的发生情况,主要心血管事件(MACE)包括心绞痛再发(RA)、支架血栓(ST),心肌梗死(MI),靶病变血运重建(TVR),卒中(Stroke),及心源性死亡(CD)。5.运用Matlab 2012a统计软件和Haploview 4.2遗传分析软件研究遗传因素,生化学因素与氯吡格雷疗效的关联。结果:1.本研究共纳入283名患者,接受CAG并PCI手术的患者172例,仅行CAG手术的患者111例,其中发生MACE的患者有34例。MAR:正常组vs MACE组MAR(42.51±12.59)%vs(50.07±13.08)%,P0.05;2.分析等位基因与MAR和MACE的关联:显性基因模型下不同基因型患者MAR比较: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,差异具有统计学意义。显性基因模型下不同基因型患者MACE发生率比较:CYP2B6 rs2279343 AA vs GG+AG,0.087 vs 0.156,P=0.039,差异具有统计学意义。以上结果提示,CYP2B6 rs2279343位点与血小板聚集率,MACE显著相关,B4GALT2 rs1061781位点与血小板聚集率显著相关。其他位点的遗传变异与MAR,MACE均无显著相关性。3.分析生化学参数与MAR和MACE的关联:生化学参数HGB,RDW-CV在CR组和非CR组比较:HGB在CR组vs非CR组,(130.18±17.34)vs(118.88±25.16),P=0.0006,RDW-CV在CR组vs非CR组,(13.56±1.32)vs(14.31±1.67),P=0.0017,MCV在MACE组与非MACE组,(91.94±6.03)vs(87.34±21.36)P=0.0456,差异有统计学意义,且变化趋势与贫血相一致,提示贫血可能影响冠心病患者氯吡格雷疗效。结论:1.CYP2B6 rs2279343、B4GALT2 rs1061781基因多态性与氯吡格雷临床疗效具有相关性。2.生化学参数HGB,RDW-CV和MCV影响氯吡格雷的抗血小板作用,提示贫血可能对氯吡格雷的疗效有影响。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与氯吡格雷临床疗效均无显著相关性。
[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.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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