BDNF基因及与其结合microRNA与中国汉族精神分裂症的关联性研究

发布时间：2018-03-22 00:13

本文选题：精神分裂症　切入点：BDNF　出处：《南京医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：从BDNF基因rs6265多态性及外周血BDNF基因mRNA表达两方面探究BDNF基因是否参与了精神分裂症的发病机制；并通过分析精神分裂症患者外周血中miR-124-3p, miR-206, miR-132的表达,来初步探讨BDNF参与精神分裂症潜在的分子调控机制；探讨精神分裂症的生物学标志与抗精神病药物治疗靶点。方法：本研究分为两部分试验,采用病例-对照研究。第一部分研究对象取自全基因组关联分析样本库(包括精神分裂症患者1407例,正常对照组1136例),利用SHE. sis软件,用拟合度χ2检验比较精神分裂症组与正常对照组之间BDNF基因rs6265多态性的基因型分布与等位基因频率分布。第二部分研究共收集符合入组标准的精神分裂症患者32例,正常健康样本48例,抽取所有样本外周静脉血5m1,利用反转录实时定量聚合酶连反应(RT-qPCR)方法测定两组样本BDNF, miR-124-3p, miR-206, miR-132的mRNA表达水平。对精神分裂症组进行PANSS量表评估,然后对所有精神分裂症患者进行单一抗精神病药物治疗,随访服用抗精神病药物12周后的精神分裂症患者,再次对其进行PANSS量表评定,然后收集样本外周静脉血,测定服药12周后精神分裂症患者BDNF,miR-124-3p, miR-206, miR-132的mRNA表达水平。本部分研究数据分析利用R软件,用t检验分析比较精神分裂症组与正常对照组,精神分裂症组与药物治疗组,以及药物组与正常对照组之间的表达水平差异。结果：1.基因表达研究样本的人口学特征无统计学差异(P0.05)。2. BDNF基因rs6265多态性基因型分布符合Hardy-Weinberg遗传平衡,精神分裂症组与正常对照组相比,rs6265多态性等位基因频率存在统计学差异(P=0.037)进一步进行性别分层,男性样本中基因型频率与等位基因频率存在统计学差异(P=0.009,P=0.003)。3.精神分裂症组与正常对照组两组外周血BDNF基因及miR-124-3p表达数据存在统计学差异(P=5.169e-05, P=5.241e-05),精神分裂症患者外周血中BDNF基因mRNA表达量显著减少,miR-124-3p表达量增多。另外两条miRNA(miR-206,miR-132)在两组样本中并未发现统计学差异(P=0.114,P=0.307)。4.经过抗精神病药物治疗12周后,精神分裂症患者经过PANSS量表评估,与基线水平相比,阴性症状与阳性症状都有了有效改善。(P0.05)5.服用抗精神病药物治疗后的患者与治疗前的基线水平相比,BDNF表达水平上调(P=1.874e-04),miR-124-3p的表达水平下调(P=0.016)。而且药物组BDNF与miR-124-3p的表达水平与正常对照组相比无统计学差异(P=0.719,P=0.183)。6.经抗精神病药物治疗的患者与治疗前的基线水平相比, miR-206,miR-132表达水平下调(P=2.863e-04,P=0.009)结论：1.BDNF基因rs6265多态性可能与中国汉族精神分裂症有一定相关性,尤其是在男性人群中。2. BDNF基因mRNA表达可能参与了精神分裂症的发病机制。BDNF基因可以作为精神分裂症诊断的候选生物学标志物和精神分裂症潜在的治疗靶点。3. miR-124-3p可以作为BDNF基因表达参与精神分裂症调控机制的强有力的预测因子。4.miR-206与miR-132表达可能未参与精神分裂症的发病机制。它们经过抗精神病药物治疗后的表达水平发生变化可能与BDNF基因表达水平变化原因无关。
[Abstract]:Objective: from the mRNA BDNF gene BDNF gene rs6265 polymorphism and expression of peripheral blood in two aspects to explore the pathogenesis of the BDNF gene is involved in schizophrenia and schizophrenia; through the analysis of miR-124-3p in peripheral blood of the patients with miR-206, the expression of miR-132, to investigate BDNF in schizophrenia molecular potential disease control mechanism; to explore the biomarker of schizophrenia and antipsychotic drug targets. Methods: This study is divided into two parts: test, a case-control study. The first part of the research object from genome-wide association analysis samples (including 1407 schizophrenic patients, 1136 cases of normal control group), using SHE. SIS software. With the chi square test to compare the fitting degree between the 2 schizophrenia group and normal control group genotype BDNF gene rs6265 polymorphism distribution and allele frequency distribution. The second part of the total collection In line with the 32 cases of schizophrenic patients group spirit, healthy 48 samples collected from all samples of peripheral venous blood 5m1, even using real time quantitative reverse transcription polymerase reaction (RT-qPCR) method for the determination of two samples of BDNF, miR-124-3p, miR-206, miR-132 mRNA expression level. The schizophrenia group PANSS table of assessment, then all schizophrenia patients were single antipsychotic treatment, follow-up of antipsychotic drugs after 12 weeks of schizophrenic patients were again PANSS scale on it, then collect samples of peripheral blood were measured after 12 weeks of therapy in patients with schizophrenia, BDNF, miR-124-3p, miR-206 the expression level of miR-132 and mRNA. The part of data analysis using R software, using t test analysis of schizophrenia group and normal control group, schizophrenia group and drug treatment group, and drug group and normal The expression difference between the control group. Results: 1. gene expression in demographic characteristics of the study sample. There were no significant differences in the distribution of.2. (P0.05) BDNF gene rs6265 polymorphisms with Hardy-Weinberg genetic equilibrium, the schizophrenia group compared with normal control group, there was significant difference in rs6265 allele frequency (P=0.037) further gender there was a significant difference between the genotype stratification, male sample frequency and allele frequency (P=0.009, P=0.003).3. schizophrenia group and normal control group two group of peripheral blood BDNF gene expression of miR-124-3p and there was a significant difference between the data (P=5.169e-05, P=5.241e-05), patients with schizophrenia BDNF gene in peripheral blood mRNA expression significantly reduced expression of miR-124-3p increased. The other two miRNA (miR-206, miR-132) did not find statistical differences in the two groups (P=0.114, P=0.307) by.4. Antipsychotic medication after 12 weeks of treatment, patients with schizophrenia by PANSS were evaluated, compared with baseline, negative and positive symptoms have been effectively improved. (P0.05) compared to the baseline level 5. antipsychotic drugs patients after the treatment and before treatment, up regulate the expression level of BDNF (P=1.874e-04), the expression level of miR-124-3p decreased (P=0.016). And the expression level of BDNF and miR-124-3p of the drug group compared with the normal control group showed no significant difference (P=0.719, P=0.183).6. after baseline in patients treated with antipsychotic treatment than before, miR-206, miR-132 expression (P=2.863e-04, P=0.009) conclusion: 1.BDNF gene rs6265 polymorphism may be associated with China schizophrenia, especially in males in the.2. BDNF mRNA gene expression.BDNF gene may be involved in the pathogenesis of schizophrenia can be As a diagnosis of schizophrenia candidate biomarkers for schizophrenia and potential therapeutic targets in.3. miR-124-3p can be used as the expression of BDNF gene in schizophrenia is a strong predictor of the regulation mechanism of.4.miR-206 and miR-132 expression may not participate in the pathogenesis of schizophrenia. Unrelated to their expression level after antipsychotic drugs after treatment the change may be related to the expression level of BDNF gene changes.

【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.3

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