PEAR1基因多态性增加中国汉族人群缺血性脑卒中患者阿司匹林抵抗易感性

发布时间：2018-03-30 08:21

  本文选题：PEAR1　切入点：阿司匹林抵抗　出处：《青岛大学》2017年硕士论文

【摘要】：背景:部分患者即使规律常规剂量服用阿司匹林,仍不能达到预期的预防效果,即实验室检测血小板活性或聚集率不能达到预期的抑制,从而增加临床心脑血管病的发生或者复发率增加,称为“阿司匹林抵抗”(AR)或阿司匹林治疗失败。近年来,遗传因素在AR中的作用,越来越受到重视。血小板内皮聚集受体-1(PEAR1)是一种新近报道的血小板跨膜蛋白,研究证明在部分种族中,PEAR1基因多态性可影响血小板聚集率,引起AR。然而全基因组关联研究(GWAS),在中国人群中尤其是缺血性脑卒中患者中,其对血小板聚集的影响报道较少。目的:探索PEAR1基因多态性与中国汉族人群缺血性脑卒中患者阿司匹林抵抗(AR)的关系。方法:纳入2015年3月至2016年3月于青岛大学附属医院住院及门诊治疗的缺血性脑卒中患者450例,均服用拜阿司匹林常规量(100mg)7天,运用血栓弹力图(TEG)技术,检测花生四烯酸(AA)诱导的血小板聚集率,即AA抑制率(AA抑制率50%为阿司匹林抵抗AR,AA抑制率≥50%为阿司匹林敏感AS),根据结果分为阿司匹林抵抗组(AR)组和阿司匹林敏感组(AS),比较两组一般临床资料。运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析两组PEAR1基因位点rs12041331,rs1256888,rs2768759单核苷酸多态性,并运用测序方法验证结果。应用Haploview4.2软件进行构建单倍型,并进行分析,运用SPSS21.0软件进行统计学分析。结果:阿司匹林抵抗发生率为24.44%,两组一般临床资料相比吸烟比例(P=0.030)差异具有统计学意义,两组基因型和等位基因频率相比,rs12041331A/G(P=0.010和P=0.011)和rs2768759A/C(P=0.030和P=0.020)差异有统计学意义。而rs1256888两组基因型和等位基因频率相比差异无统计学意义。将所有危险因素均纳入多因素Logistic回归分析,显示rs12041331GG基因型是AR发生的独立危险因素,携带GG基因型患者AR发生率更高,吸烟亦是AR独立危险因素。(OR=3.143,CI95%=1.004-9.834,P=0.027),而位点rs2768759无统计学意义。应用Haploview4.2软件进行单倍型分析显示,三个位点(rs12041331,rs1256888,rs2768759)三者之间及两两之间,只有rs12041331和rs1256888可构成单倍型(TG,GA,GG)(R2=0.818,D’=0.972),其中,单倍型TG可增加AR的发生风险(P=0.018,OR=1.390,CI95%=1.008-2.010)。结论:PEAR1位点rs12041331,rs1256888基因多态性与中国汉族人群缺血性脑卒中患者阿司匹林抵抗(AR)有关,rs12041331GG基因型及吸烟是阿司匹林抵抗的独立危险因素。单倍型TG可增加AR的发生风险。
[Abstract]:Background: even if regular routine doses of aspirin were taken, some patients could not achieve the desired preventive effect, that is, the laboratory test of platelet activity or aggregation rate could not achieve the expected inhibition.Thus increasing the incidence or recurrence rate of clinical cardiovascular and cerebrovascular disease, known as "aspirin resistance" or aspirin treatment failure.In recent years, more and more attention has been paid to the role of genetic factors in AR.Platelet endothelial aggregation receptor-1 / PEAR1 is a recently reported platelet-transmembrane protein. It has been shown that the polymorphism of PEAR1 gene may affect platelet aggregation rate and cause ARs in some ethnic groups.However, the effect of GWASA on platelet aggregation in Chinese population, especially in ischemic stroke patients, is less reported.Objective: to explore the relationship between PEAR1 gene polymorphism and aspirin resistance to AR1 in ischemic stroke patients in Chinese Han population.Methods: from March 2015 to March 2016, 450 patients with ischemic stroke were enrolled in hospital and outpatient treatment of Qingdao University. All patients were treated with Aspirin (100 mg / g) for 7 days, and thromboelastography (TEG) technique was used.The platelet aggregation rate induced by AAA was measured.That is to say, 50% of AA inhibition rate is aspirin resistance to ARN AA inhibition rate 鈮，

本文编号：1685088