本文選題：COX-I + 單核苷酸多態(tài)性　； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景及目的:阿司匹林是臨床上缺血性卒中二級預(yù)防使用最為廣泛的藥物。盡管常規(guī)服用治療劑量的阿司匹林作為缺血性卒中的二級預(yù)防,臨床上仍有一部分患者對阿司匹林反應(yīng)不足,并出現(xiàn)不良結(jié)局,這種現(xiàn)象稱為“阿司匹林抵抗”。遺傳因素和環(huán)境因素可能獨自或者共同在其中扮演著重要的角色。環(huán)氧化酶-1(Cyclooxygenase-1,COX-1)作為阿司匹林的直接作用靶點,其編碼基因COX-1的遺傳變異可能導(dǎo)致對阿司匹林不敏感。而吸煙作為一種重要的環(huán)境危險因素,與人體多種疾病存在相關(guān)性。然而,二者是否存在交互作用,以及交互作用的程度如何,是否會對服用阿司匹林的卒中患者預(yù)后產(chǎn)生不良影響目前仍不清楚。本課題目的是建立中國漢族服用阿司匹林的缺血性卒中隊列,分析COX-1基因多態(tài)性、吸煙以及二者的交互作用對缺血性卒中患者功能預(yù)后的影響。方法:基于南京卒中注冊系統(tǒng),提取2009年12月份到2012年10月份服用阿司匹林的急性缺血性卒中患者,入組條件為:1)中國漢族人群;2)年齡≥18歲;3)神經(jīng)功能缺失癥狀持續(xù)超過24小時并有影像學(xué)證據(jù)證明為急性缺血性卒中;4)癥狀發(fā)生48小時內(nèi)服用阿司匹林腸溶片(100mg/d);5)本次卒中發(fā)病前改良Rankin量表(modified Rankin Scale,mRS)評分≤1分;6)同意入組本研究并留有合格的血標(biāo)本。排除標(biāo)準(zhǔn)為:1)同時服用抗凝藥、非甾體類抗炎藥或者服用除阿司匹林外的其他抗血小板藥物;2)根據(jù)TOAST分型標(biāo)準(zhǔn)定義為心源性卒中;3)90天隨訪結(jié)束前終止或改變抗血小板治療方案;4)有出血史或血液系統(tǒng)疾病;5)惡性腫瘤;6)嚴(yán)重肝、腎功能不全。采用改良多重連接酶檢測反應(yīng)(Improved Multiple Ligase Detection Reaction,iMLDR)方法對三個COX-1基因的單核苷酸多態(tài)性位點(Single nucleotide polymorphisms,SNPs)rs1330344,rs3842788和rs5788進(jìn)行基因分型。不良功能預(yù)后定義為90天mRS評分3-6分。通過Logistic回歸、單倍型分析、交互作用分析等統(tǒng)計學(xué)方法評估COX-1基因多態(tài)性、COX-1基因-吸煙交互作用與功能預(yù)后的相關(guān)性。結(jié)果:本研究共納入617名患者,其中145名(23.5%)患者出現(xiàn)不良功能預(yù)后。采用Logistic回歸方法校正年齡、性別、高血壓、國立衛(wèi)生院神經(jīng)功能評分(National Institute of Health Stroke Scale,NIHSS)等變量后,rs1330344的 CC 基因型與不良功能預(yù)后相關(guān)(RR= 1.73;95%CI:1.17-2.37)。同樣,CGC單倍型也得到類似結(jié)果(RR= 1.40;95%CI:1.08-1.77)。交互分析發(fā)現(xiàn),rs1330344和吸煙之間(P交互= 0.018)以及COX-1單倍型和吸煙之間(P交互 =0.040)均存在顯著的交互作用。結(jié)論:在中國漢族服用阿司匹林的缺血性卒中患者中,COX-1基因多態(tài)性與吸煙可能存在交互作用,增加不良功能預(yù)后風(fēng)險。COX-1基因-吸煙交互作用可以部分解釋服用阿司匹林患者預(yù)后的異質(zhì)性。
[Abstract]:Background and objective: aspirin is the most widely used drug for secondary prevention of ischemic stroke. Despite the routine dose of aspirin as a secondary prevention of ischemic stroke, some patients still respond inadequately to aspirin and have adverse outcomes, a phenomenon known as aspirin resistance. Genetic and environmental factors may play an important role alone or together. Cyclooxygenase-1 cyclooxygenase-1 (COX-1) is a direct target of aspirin. The genetic variation of its encoding gene COX-1 may lead to insensitivity to aspirin. As an important environmental risk factor, smoking is associated with many diseases. However, it is not clear whether there is interaction and the extent of the interaction, and whether it will have a negative impact on the prognosis of stroke patients taking aspirin. The aim of this study was to establish a cohort of patients with ischemic stroke taking aspirin in Chinese Han nationality, and to analyze the effects of COX-1 gene polymorphism, smoking and their interaction on the functional prognosis of ischemic stroke patients. Methods: acute ischemic stroke patients who took aspirin from December 2009 to October 2012 were extracted from Nanjing Stroke Registration system. Admission condition: 1) Chinese Han population (2) Age 鈮，

本文編號：1797678