中国汉族人口中GAB2基因中的单核苷酸多态位点rs3740677与迟发型AD的关系

发布时间：2018-03-06 04:19

本文选题：生长因子受体结合蛋白-2的相关结合蛋白基因　切入点：迟发型阿尔茨海默病　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:本研究旨在探索生长因子受体结合蛋白-2的相关结合蛋白家族基因中的一个mi RNAs-185特异性靶向关联序列中的单核苷酸多态位点(SNPs)rs3740677与迟发型阿尔茨海默病(LOAD)发病的具体关联。方法:我们通过大样本病例对照研究,从青岛市立医院在内山东省内多家公立医院神经内科选取992例LOAD患者作为病例组,同时从青岛市立医院查体中心等多家合作医院选取1358健康正常人作为对照组,提取所有受试者外周血DNA。通过生物信息学方法从多个公开的生物学信息库中在目前已报道的所有在AD脑内差异表达的3’UTR mi RNAs的靶基因中筛选出在汉族人群中常见的AD易感基因GAB2,并用最终确定了3’UTR mi RNAs-185的特异性靶向序列中的一个常见的单核苷酸多态位点rs3740677。并利用多重高温连接酶检测反应(i MLDR)技术进行了相关基因分型。此外,我们还应用等位基因特异性多重PCR(Multi-ARMS)技术进行了APOE基因分型。最后我们应用SPSS19.0软件,采取t检验、卡方检验及Logistic回归分析等方法对相关数据进行统计学分析,得到相关统计学检验值:P值,OR值及其95%可信区间等,进而判断此SNP位点与北方汉族人群迟发性AD发病的可能关系。结果:GAB2 SNP rs3740677基因型显示等位基因“T”为最小频率等位基因。通过卡方检验,我们发现GAB2 SNP rs3740677的基因型与最小等位基因T在LOAD病例组与健康对照组间均存在显著统计学差异(基因型P=0.024;等位基因P=0.008)。此外,作为GAB2 SNP rs3740677的预期风险等位基因T,我们的卡方检验分析发现其可能对LOAD发病具有保护性作用(OR=0.833,95%CI=0.728-0.952)。通过对LOAD病例组以及健康对照组人群行进一步的APOEε4携带与否分层,我们通过卡方检验分析发现:无论在APOEε4+(携带)还是APOEε4-(非携带)条件下均未发现GAB2 SNP rs3740677基因型与最小等位基因T分布在两组间存在统计学差异(APOEε4+:基因型P=0.437,等位基因P=0.208;APOEε4-:基因型P=0.149,等位基因P=0.064)。此外,在经过发病年龄或检测年龄、性别、APOEε4携带状态等因素调整后,我们通过逻辑学回归分析检测了三个基因型遗传模态中的GAB2 SNP rs3740677基因型在两组中的分布差异。最终结果显示:在显性遗传模态以及叠加模态中发现了GAB2SNP rs3740677基因型分布的统计学差异,并且同样呈现一种对AD发病的保护性作用。而在隐性遗传模态中我们并未发现任何统计学意义(显性遗传模态:OR=0.831,95%CI=0.702 0.983,P=0.031;叠加模态:OR=0.855,95%CI=0.745 0.983,P=0.027;隐性遗传模态:P=0.252)。此外,我们更进一步的检测的三种模态中基因型分布与APOEε4状态的可能交互作用。最终,均未发现统计学意义。结论:我们的研究在北方汉族人群中首次证实了AD相关基因GAB2中一个3’UTR mi RNAs-185的特异性靶向序列中的常见SNPs rs3740677与LOAD发病的显著关联。而且SNPs rs3740677被进一步提示是一种对LOAD发病具有保护性作用的影响因素。
[Abstract]:Objective: to explore the single nucleotide polymorphism (SNPs) rs3740677 and late onset Alzheimer's disease (Lod) in a mi RNAs-185 specific target sequence of the associated protein family of growth factor receptor-binding protein -2. Methods: through a large sample case-control study, From the Department of Neurology of many public hospitals in Shandong Province, Qingdao Municipal Hospital, 992 patients with LOAD were selected as the case group, while 1358 healthy healthy people were selected as the control group from various cooperative hospitals, such as the physical examination center of Qingdao Municipal Hospital. All subjects' peripheral blood DNAs were extracted by bioinformatics. Common in Han population was screened from a number of open biological information databases from all reported target genes of 3UTR mi RNAs differentially expressed in AD brain. GAB2, a common single nucleotide polymorphic site rs3740677, was finally identified in the specific target sequence of 3UTR mi RNAs-185. The related genotyping was performed by multiplex high temperature ligase detection reaction I MLDR. We also used allele-specific multiplex APOE genotyping. Finally, we used SPSS19.0 software, t-test, chi-square test and Logistic regression analysis to analyze the relevant data statistically. The correlation statistical test value, the OR value and the confidence interval of 95%, etc., were obtained. The possible relationship between the SNP locus and the onset of delayed AD in northern Han population was determined. Results the gene "T" was the least frequent allele in the G _ AB2 SNP rs3740677 genotype. We found that the genotype and minimum allele T of GAB2 SNP rs3740677 were significantly different between the LOAD case group and the healthy control group. As the expected risk allele of GAB2 SNP rs3740677, our chi-square test analysis showed that it may have protective effect on the pathogenesis of LOAD. Further stratification of APOE 蔚 4 carrying or not was performed in LOAD case group and healthy control group. By chi-square test, we found that there was no statistical difference between GAB2 SNP rs3740677 genotype and minimum allele T distribution under APOE 蔚 4 (carrying) or APOE 蔚 4 (non-carrier) conditions. There was statistical difference between the two groups in the distribution of GAB2 SNP rs3740677 genotype (P < 0. 437) and allele (P < 0. 437). In addition, the gene PX 0.208 AAPOE 蔚 4: genotype PX 0.149, allele Pn0. 064, in addition, After adjustment of age of onset, age of detection, sex of APOE 蔚 4, and so on, We detected the distribution differences of GAB2SNP rs3740677 genotypes in the three genotypes by logistic regression analysis. The final results showed that the GAB2SNP rs3740677 genotypes were found in dominant genetic modes and superposition modes. Statistical differences in distribution, And there is also a protective effect on AD, and we have not found any statistical significance in recessive genetic mode. (dominant genetic mode: OR0. 831 / 95CIQ 0.702 0.983 P0. 031; superposition mode: 0. 855 / 95CIN 0.745 / 0.983P0.027; recessive genetic mode: P0. 252). We further examined the possible interaction between genotype distribution and APOE 蔚 4 status in the three modes we examined. Conclusion: our study has confirmed for the first time in the northern Han population that the common SNPs rs3740677 in the specific target sequence of 3UTR mi RNAs-185 in the AD related gene GAB2 is significantly associated with the pathogenesis of LOAD. Rs3740677 is further suggested to be a protective factor in the pathogenesis of LOAD.
【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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