中国北方汉族人群FERMT2基因rs17125944多态性与阿尔茨海默病发病风险的关系

发布时间：2018-03-07 16:55

本文选题：阿尔茨海默病　切入点：FERMT2基因　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的阿尔茨海默病(Alzheimer disease,AD)是发生于老年期,以不可逆的认知功能及行为损害为特征的中枢神经系统退行性病变。以发病年龄来看,阿尔茨海默病分为早发型阿尔茨海默病(early-onset Alzheimer disease,EOAD)和迟发型阿尔茨海默病(1ate-onset Alzheimer disease,LOAD),其中以迟发型阿尔茨海默病占大多数。在遗传方式上,早发型阿尔茨海默病通常为常染色体显性遗传;而迟发型阿尔茨海默病遗传方式更加复杂,环境因素和遗传因素及其二者相互作用都可能影响LOAD的发生和发展。现已发现众多的候选基因与迟发型阿尔茨海默病的发病风险相关联。本研究旨在分析在北方汉族人群中Fermitin家族的同源物2(FERMT2)基因位点rs17125944的多态性与迟发型阿尔茨海默病发病风险的关系。方法应用病例一对照研究的方法,选取2338名北方汉族人群受试者作为研究对象,其中有984例晚发性阿尔茨海默病(LOAD)患者和1354例与其年龄和性别相匹配的健康对照。根据最近在高加索人群中一项全基因组关联研究(GWAS)的meta分析中发现了数个新的易感基因位点与迟发型阿尔茨海默病(LOAD)的发病风险相关。我们从中选取1个基因位点(rs17125944),利用多重单核苷酸多态性(SNP)分型技术SNPscanTM对FERMT2基因位点rs17125944进行基因分型。同时,利用改进的多重连接酶检测反应(i MLDR)进行apolipoprotein E(APOE)基因分型。在统计方法上,应用Student-t检验、卡方检验对受试者的一般特征、基因型及等位基因进行比较,进一步在校正了性别、年龄和APOEε4等位基因后,利用Logistic回归来分析rs17125944多态性与LOAD发病风险的关系。另外,我们将最近在不同人群中探讨FERMT2基因位点rs17125944多态性与LOAD关系的研究与我们现在的研究进行meta分析,进一步探讨rs17125944多态性与阿尔茨海默病发病风险的关系。结果FERMT2基因位点rs17125944等位基因频率和基因型分布在LOAD组和对照组均没有显著差异(分别是P=0.975,P=0.953)。将样本按APOEε4分层后,FERMT2基因位点rs17125944等位基因频率和基因型分布在LOAD组和对照组中同样没有显著差异(携带APOEε4组分别为P=0.377,P=0.398;未携带APOEε4组分别为P=0.586,P=0.395)。另外经Logistic回归分析去除混杂因素(年龄、性别、APOEε4)影响后,FERMT2基因rs17125944多态性与LOAD发病风险在三种模型中均无相关性(显性模型P=0.766,叠加模型P=0.937,隐性模型P=0.647)。将相关研究数据进行meta分析后的结果为在汉族人群中最小等位基因C与LOAD的发病风险没有相关性(OR=1.07,95%CI=0.89 1.28)。结论在北方汉族人群中,FERMT2基因位点rs17125944的多态性可能与阿尔茨海默病的发病风险没有相关性。但这一结论还需要在更大的样本量和不同种族人群中去进一步验证。同时,关于FERMT2基因在人体中如何参与tau蛋白毒性及淀粉样前体蛋白(amyloid precursor protein,APP)代谢的确切机制还需要进一步研究。
[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.
【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】：R749.16

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