發(fā)布時間：2018-03-07 16:55

  本文選題：阿爾茨海默病　切入點：FERMT2基因　出處：《青島大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的阿爾茨海默病(Alzheimer disease,AD)是發(fā)生于老年期,以不可逆的認(rèn)知功能及行為損害為特征的中樞神經(jīng)系統(tǒng)退行性病變。以發(fā)病年齡來看,阿爾茨海默病分為早發(fā)型阿爾茨海默病(early-onset Alzheimer disease,EOAD)和遲發(fā)型阿爾茨海默病(1ate-onset Alzheimer disease,LOAD),其中以遲發(fā)型阿爾茨海默病占大多數(shù)。在遺傳方式上,早發(fā)型阿爾茨海默病通常為常染色體顯性遺傳;而遲發(fā)型阿爾茨海默病遺傳方式更加復(fù)雜,環(huán)境因素和遺傳因素及其二者相互作用都可能影響LOAD的發(fā)生和發(fā)展�，F(xiàn)已發(fā)現(xiàn)眾多的候選基因與遲發(fā)型阿爾茨海默病的發(fā)病風(fēng)險相關(guān)聯(lián)。本研究旨在分析在北方漢族人群中Fermitin家族的同源物2(FERMT2)基因位點rs17125944的多態(tài)性與遲發(fā)型阿爾茨海默病發(fā)病風(fēng)險的關(guān)系。方法應(yīng)用病例一對照研究的方法,選取2338名北方漢族人群受試者作為研究對象,其中有984例晚發(fā)性阿爾茨海默病(LOAD)患者和1354例與其年齡和性別相匹配的健康對照。根據(jù)最近在高加索人群中一項全基因組關(guān)聯(lián)研究(GWAS)的meta分析中發(fā)現(xiàn)了數(shù)個新的易感基因位點與遲發(fā)型阿爾茨海默病(LOAD)的發(fā)病風(fēng)險相關(guān)。我們從中選取1個基因位點(rs17125944),利用多重單核苷酸多態(tài)性(SNP)分型技術(shù)SNPscanTM對FERMT2基因位點rs17125944進行基因分型。同時,利用改進的多重連接酶檢測反應(yīng)(i MLDR)進行apolipoprotein E(APOE)基因分型。在統(tǒng)計方法上,應(yīng)用Student-t檢驗、卡方檢驗對受試者的一般特征、基因型及等位基因進行比較,進一步在校正了性別、年齡和APOEε4等位基因后,利用Logistic回歸來分析rs17125944多態(tài)性與LOAD發(fā)病風(fēng)險的關(guān)系。另外,我們將最近在不同人群中探討FERMT2基因位點rs17125944多態(tài)性與LOAD關(guān)系的研究與我們現(xiàn)在的研究進行meta分析,進一步探討rs17125944多態(tài)性與阿爾茨海默病發(fā)病風(fēng)險的關(guān)系。結(jié)果FERMT2基因位點rs17125944等位基因頻率和基因型分布在LOAD組和對照組均沒有顯著差異(分別是P=0.975,P=0.953)。將樣本按APOEε4分層后,FERMT2基因位點rs17125944等位基因頻率和基因型分布在LOAD組和對照組中同樣沒有顯著差異(攜帶APOEε4組分別為P=0.377,P=0.398;未攜帶APOEε4組分別為P=0.586,P=0.395)。另外經(jīng)Logistic回歸分析去除混雜因素(年齡、性別、APOEε4)影響后,FERMT2基因rs17125944多態(tài)性與LOAD發(fā)病風(fēng)險在三種模型中均無相關(guān)性(顯性模型P=0.766,疊加模型P=0.937,隱性模型P=0.647)。將相關(guān)研究數(shù)據(jù)進行meta分析后的結(jié)果為在漢族人群中最小等位基因C與LOAD的發(fā)病風(fēng)險沒有相關(guān)性(OR=1.07,95%CI=0.89 1.28)。結(jié)論在北方漢族人群中,FERMT2基因位點rs17125944的多態(tài)性可能與阿爾茨海默病的發(fā)病風(fēng)險沒有相關(guān)性。但這一結(jié)論還需要在更大的樣本量和不同種族人群中去進一步驗證。同時,關(guān)于FERMT2基因在人體中如何參與tau蛋白毒性及淀粉樣前體蛋白(amyloid precursor protein,APP)代謝的確切機制還需要進一步研究。
[Abstract]:Objective Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system characterized by irreversible cognitive and behavioral impairment in the elderly. Alzheimer's disease is divided into early-onset Alzheimer's Alzheimer disease (EOADA) and late-onset Alzheimer's disease (1ate-onset Alzheimer disease). Early onset Alzheimer's disease is usually autosomal dominant; late onset Alzheimer's is more complex. Environmental and genetic factors and their interactions may affect the occurrence and development of LOAD. A large number of candidate genes have been found to be associated with the risk of delayed Alzheimer's disease. The relationship between the polymorphism of rs17125944 in the homologue 2FERMT2 of Fermitin family and the risk of delayed Alzheimer's disease in Han population. Methods A case-control study was used. 2338 subjects of Han nationality in northern China were selected as the subjects. Among them, 984 patients with late onset Alzheimer's disease (Lod) and 1354 healthy controls matched their age and sex. Several new GWASs were found in meta analysis of a recent genome-wide association study in Caucasian populations. Susceptibility loci were associated with the risk of late onset Alzheimer's disease (Lod). We selected one locus, rs17125944, and used multiple single nucleotide polymorphisms (SNPscanTM) to type rs17125944 at FERMT2 locus. In statistical method, Student-t test and chi-square test were used to compare the general characteristics, genotypes and alleles of the subjects. After age and APOE 蔚 4 allele, Logistic regression was used to analyze the relationship between rs17125944 polymorphism and the risk of LOAD. We will explore the relationship between rs17125944 polymorphism of FERMT2 locus and LOAD in different populations, and we will do meta analysis in our current study. The relationship between rs17125944 polymorphism and risk of Alzheimer's disease was further investigated. Results there was no significant difference in the frequency and genotype distribution of rs17125944 allele in FERMT2 locus between the LOAD group and the control group (P0. 975% P0. 953). The samples were stratified according to APOE 蔚 4. There was no significant difference in rs17125944 allele frequency and genotype distribution between LOAD group and control group (the APOE 蔚 4 group was 0.377Pu 0.398, the APOE 蔚 4 group was 0.586PU 0.395N), and the confounding factors (age, age, age) were removed by Logistic regression analysis, and the frequency and genotype distribution of FERMT2 allele were not significantly different between the LOAD group and the control group (P < 0.05). There was no correlation between the rs17125944 polymorphism of FERMT2 gene and the risk of LOAD in the three models (dominant model P0. 766, superposition model Pu 0. 937, recessive model P0. 647 7). The results of meta analysis showed that FERMT2 gene polymorphism was the most significant in Han population. There was no correlation between small allele C and the risk of LOAD. Conclusion the polymorphism of FERMT2 locus rs17125944 may not be associated with the risk of Alzheimer's disease in northern Han population. Large samples and different ethnic groups to further verify. At the same time, The exact mechanism of FERMT2 gene involved in tau protein toxicity and amyloid precursor protein (app) metabolism needs further study.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.16

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