發(fā)布時(shí)間：2018-03-30 08:21

  本文選題：PEAR1　切入點(diǎn)：阿司匹林抵抗　出處：《青島大學(xué)》2017年碩士論文

【摘要】：背景:部分患者即使規(guī)律常規(guī)劑量服用阿司匹林,仍不能達(dá)到預(yù)期的預(yù)防效果,即實(shí)驗(yàn)室檢測(cè)血小板活性或聚集率不能達(dá)到預(yù)期的抑制,從而增加臨床心腦血管病的發(fā)生或者復(fù)發(fā)率增加,稱為“阿司匹林抵抗”(AR)或阿司匹林治療失敗。近年來(lái),遺傳因素在AR中的作用,越來(lái)越受到重視。血小板內(nèi)皮聚集受體-1(PEAR1)是一種新近報(bào)道的血小板跨膜蛋白,研究證明在部分種族中,PEAR1基因多態(tài)性可影響血小板聚集率,引起AR。然而全基因組關(guān)聯(lián)研究(GWAS),在中國(guó)人群中尤其是缺血性腦卒中患者中,其對(duì)血小板聚集的影響報(bào)道較少。目的:探索PEAR1基因多態(tài)性與中國(guó)漢族人群缺血性腦卒中患者阿司匹林抵抗(AR)的關(guān)系。方法:納入2015年3月至2016年3月于青島大學(xué)附屬醫(yī)院住院及門(mén)診治療的缺血性腦卒中患者450例,均服用拜阿司匹林常規(guī)量(100mg)7天,運(yùn)用血栓彈力圖(TEG)技術(shù),檢測(cè)花生四烯酸(AA)誘導(dǎo)的血小板聚集率,即AA抑制率(AA抑制率50%為阿司匹林抵抗AR,AA抑制率≥50%為阿司匹林敏感AS),根據(jù)結(jié)果分為阿司匹林抵抗組(AR)組和阿司匹林敏感組(AS),比較兩組一般臨床資料。運(yùn)用聚合酶鏈反應(yīng)-限制性片段長(zhǎng)度多態(tài)性(PCR-RFLP)技術(shù)分析兩組PEAR1基因位點(diǎn)rs12041331,rs1256888,rs2768759單核苷酸多態(tài)性,并運(yùn)用測(cè)序方法驗(yàn)證結(jié)果。應(yīng)用Haploview4.2軟件進(jìn)行構(gòu)建單倍型,并進(jìn)行分析,運(yùn)用SPSS21.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:阿司匹林抵抗發(fā)生率為24.44%,兩組一般臨床資料相比吸煙比例(P=0.030)差異具有統(tǒng)計(jì)學(xué)意義,兩組基因型和等位基因頻率相比,rs12041331A/G(P=0.010和P=0.011)和rs2768759A/C(P=0.030和P=0.020)差異有統(tǒng)計(jì)學(xué)意義。而rs1256888兩組基因型和等位基因頻率相比差異無(wú)統(tǒng)計(jì)學(xué)意義。將所有危險(xiǎn)因素均納入多因素Logistic回歸分析,顯示rs12041331GG基因型是AR發(fā)生的獨(dú)立危險(xiǎn)因素,攜帶GG基因型患者AR發(fā)生率更高,吸煙亦是AR獨(dú)立危險(xiǎn)因素。(OR=3.143,CI95%=1.004-9.834,P=0.027),而位點(diǎn)rs2768759無(wú)統(tǒng)計(jì)學(xué)意義。應(yīng)用Haploview4.2軟件進(jìn)行單倍型分析顯示,三個(gè)位點(diǎn)(rs12041331,rs1256888,rs2768759)三者之間及兩兩之間,只有rs12041331和rs1256888可構(gòu)成單倍型(TG,GA,GG)(R2=0.818,D’=0.972),其中,單倍型TG可增加AR的發(fā)生風(fēng)險(xiǎn)(P=0.018,OR=1.390,CI95%=1.008-2.010)。結(jié)論:PEAR1位點(diǎn)rs12041331,rs1256888基因多態(tài)性與中國(guó)漢族人群缺血性腦卒中患者阿司匹林抵抗(AR)有關(guān),rs12041331GG基因型及吸煙是阿司匹林抵抗的獨(dú)立危險(xiǎn)因素。單倍型TG可增加AR的發(fā)生風(fēng)險(xiǎn)。
[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，

本文編號(hào)：1685088