多药物耐药基因多态性与缺血性脑卒中患者阿司匹林抵抗的相关性
发布时间:2018-03-04 11:30
本文选题:多药物耐药基因 切入点:P-糖蛋白 出处:《青岛大学》2017年硕士论文 论文类型:学位论文
【摘要】:目的探讨多药物耐药(Multi-drug resistance,ABCB1/MDR1)基因三个位点C1236T、G2677T/A、C3435T的单核苷酸多态性(single nucleotide polymorphisms,SNP)与缺血性脑卒中患者阿司匹林抵抗(Aspirin resistance,AR)的关系。方法本研究连续纳入2014年9月至2016年5月在青岛大学附属医院神经内科住院的脑梗死患者300例为研究人群,入组患者均符合中国急性缺血性脑卒中诊治指南的诊断标准,临床上并经头颅MRI或CT检查确诊,所有患者均规律口服阿司匹林(100mg)7天以上抗血小板治疗,后根据血栓弹力图(blood clots elastic figure,TEG)检测花生四烯酸(AA)诱导的血小板聚集抑制率(%)将研究人群分为阿司匹林抵抗组(AR)75例,即AA抑制率50%;阿司匹林敏感组(Aspirin sensitive,AS)225例,即AA抑制率≥50%。采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)和直接测序方法,对两组研究人群的ABCB1单核苷酸多态性位点C1236T、G2677T/A、C3435T进行分析,探讨ABCB1三位点多态性及其单倍型与缺血性脑卒中患者AR的关系。结果在本研究中ABCB1 C3435T位点的T等位基因频率在AR组和AS组中分别为57.3%和43.1%,差异有统计学意义(χ2=9.143,p=0.002),且AR组中(CT+TT)基因型高于AS组,差异亦有统计学意义(χ2=4.369,p=0.037);而对于ABCB1 C1236T和G2677T/A等位基因频率及基因型分布在两组间差异均无统计学意义(p0.05);单倍型(C-T-T)的OR值为1.602(χ2=5.374,p=0.02),单倍型(C-G-C)的OR值为0.49(χ2=8.775,p=0.003),单倍型(T-G-C)的OR值为3.010(χ2=5.846,p=0.015),单倍型(T-T-T)的OR值为3.30(χ2=4.650,p=0.031),差异具有统计学意义,其中单倍型(C-T-T,T-G-C,T-T-T)可增加缺血性脑卒中患者AR的发生风险。结论ABCB1基因C3435T单核苷酸多态性与缺血性脑卒中患者AR有关;C1236T和G2677T/A单核苷酸多态性与AR无关;单倍型(C-T-T,T-G-C,T-T-T)可能会增加缺血性脑卒中患者AR的发生风险。
[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.
【学位授予单位】:青岛大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R743.3
【参考文献】
相关期刊论文 前1条
1 ;Cyclooxygenase 2 polymorphism and colorectal cancer:-765G>C variant modifies risk associated with smoking and body mass index[J];World Journal of Gastroenterology;2008年11期
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