本文選題：多藥物耐藥基因　切入點：P-糖蛋白　出處：《青島大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的探討多藥物耐藥(Multi-drug resistance,ABCB1/MDR1)基因三個位點C1236T、G2677T/A、C3435T的單核苷酸多態(tài)性(single nucleotide polymorphisms,SNP)與缺血性腦卒中患者阿司匹林抵抗(Aspirin resistance,AR)的關(guān)系。方法本研究連續(xù)納入2014年9月至2016年5月在青島大學附屬醫(yī)院神經(jīng)內(nèi)科住院的腦梗死患者300例為研究人群,入組患者均符合中國急性缺血性腦卒中診治指南的診斷標準,臨床上并經(jīng)頭顱MRI或CT檢查確診,所有患者均規(guī)律口服阿司匹林(100mg)7天以上抗血小板治療,后根據(jù)血栓彈力圖(blood clots elastic figure,TEG)檢測花生四烯酸(AA)誘導的血小板聚集抑制率(%)將研究人群分為阿司匹林抵抗組(AR)75例,即AA抑制率50%;阿司匹林敏感組(Aspirin sensitive,AS)225例,即AA抑制率≥50%。采用聚合酶鏈反應-限制性片段長度多態(tài)性技術(shù)(PCR-RFLP)和直接測序方法,對兩組研究人群的ABCB1單核苷酸多態(tài)性位點C1236T、G2677T/A、C3435T進行分析,探討ABCB1三位點多態(tài)性及其單倍型與缺血性腦卒中患者AR的關(guān)系。結(jié)果在本研究中ABCB1 C3435T位點的T等位基因頻率在AR組和AS組中分別為57.3%和43.1%,差異有統(tǒng)計學意義(χ2=9.143,p=0.002),且AR組中(CT+TT)基因型高于AS組,差異亦有統(tǒng)計學意義(χ2=4.369,p=0.037);而對于ABCB1 C1236T和G2677T/A等位基因頻率及基因型分布在兩組間差異均無統(tǒng)計學意義(p0.05);單倍型(C-T-T)的OR值為1.602(χ2=5.374,p=0.02),單倍型(C-G-C)的OR值為0.49(χ2=8.775,p=0.003),單倍型(T-G-C)的OR值為3.010(χ2=5.846,p=0.015),單倍型(T-T-T)的OR值為3.30(χ2=4.650,p=0.031),差異具有統(tǒng)計學意義,其中單倍型(C-T-T,T-G-C,T-T-T)可增加缺血性腦卒中患者AR的發(fā)生風險。結(jié)論ABCB1基因C3435T單核苷酸多態(tài)性與缺血性腦卒中患者AR有關(guān);C1236T和G2677T/A單核苷酸多態(tài)性與AR無關(guān);單倍型(C-T-T,T-G-C,T-T-T)可能會增加缺血性腦卒中患者AR的發(fā)生風險。
[Abstract]:Objective to investigate the relationship between the single nucleotide polymorphisms (SNPs) and aspirin resistance to Aspirin in patients with ischemic stroke from September 2014 to May 2016 in three loci of the multidrug resistance multidrug resistance ABCB1 / MDR1) gene, C1236TN G2677T / Agna C3435T. 300 inpatients with cerebral infarction in Department of Neurology, affiliated Hospital of Island University, were studied. All the patients in the group met the diagnostic criteria of Chinese guidelines for the diagnosis and treatment of acute ischemic stroke. All patients were diagnosed clinically by MRI or CT. All patients were regularly treated with aspirin for more than 7 days. Then according to thromboelastography clots elastic configuration test, the inhibition rate of platelet aggregation induced by arachidonic acid (AAA) was measured. The subjects were divided into aspirin resistance group (75 cases, AA inhibition rate 50%), aspirin sensitive group (Aspirin sensitive group, 225 cases), Aspirin sensitive group, Aspirin sensitive group, Aspirin sensitive group, Aspirin sensitive group, Aspirin sensitive group, Aspirin sensitive group, and Aspirin sensitive group. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods, the ABCB1 single nucleotide polymorphism (SNP) C1236TG2677T / AC3435T was analyzed. To investigate the relationship between ABCB1 trilocus polymorphism and haplotype and AR in ischemic stroke patients. Results in this study, the T allele frequencies of ABCB1 C3435T locus in AR group and as group were 57.3% and 43.1, respectively. The difference was statistically significant (蠂 ~ 2 ~ (9.143) P ~ (0.002), P ~ (0.002)). The genotype of CT TTT in AR group was higher than that in as group. The difference was also statistically significant (蠂 2 / 4.369p = 0.0373N), but for ABCB1 C1236T and G2677T / A allele frequency and genotype distribution, the OR value of haplotype C-T-T was 1.602 (蠂 25.374p 0.02U, 蠂 25.374p 0.02n), OR value of haplotype C-G-Cwas 0.49 (蠂 ~ 28.775p ~ (3), T _ (G-C) = 3.010 (蠂 ~ (25.846) P 0.015), P < 0.05), no significant difference was found between the two groups (蠂 ~ (2)) (蠂 ~ (2)) (蠂 ~ (2)) (蠂 ~ (8.775) P < 0.05), the OR of haplotype T-G-Cwas 3.010 (蠂 ~ (5.8446) p0. 015). The OR value of haplotype T-T was 3.30 (蠂 ~ 2 = 4.650) and the difference was statistically significant. Haplotype C T T T G G C T T T) can increase the risk of AR in patients with ischemic stroke. Conclusion the single nucleotide polymorphism of ABCB1 gene C3435T is not associated with AR in patients with ischemic stroke, C1236T and G2677T / A single nucleotide polymorphisms are not associated with AR. Haplotype C-T-T-T-G-G-T-T-T-T may increase the risk of AR in patients with ischemic stroke.
【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R743.3

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相關(guān)期刊論文 前1條

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本文編號：1565460