本文選題：生長(zhǎng)因子受體結(jié)合蛋白-2的相關(guān)結(jié)合蛋白基因　切入點(diǎn)：遲發(fā)型阿爾茨海默病　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:本研究旨在探索生長(zhǎng)因子受體結(jié)合蛋白-2的相關(guān)結(jié)合蛋白家族基因中的一個(gè)mi RNAs-185特異性靶向關(guān)聯(lián)序列中的單核苷酸多態(tài)位點(diǎn)(SNPs)rs3740677與遲發(fā)型阿爾茨海默病(LOAD)發(fā)病的具體關(guān)聯(lián)。方法:我們通過(guò)大樣本病例對(duì)照研究,從青島市立醫(yī)院在內(nèi)山東省內(nèi)多家公立醫(yī)院神經(jīng)內(nèi)科選取992例LOAD患者作為病例組,同時(shí)從青島市立醫(yī)院查體中心等多家合作醫(yī)院選取1358健康正常人作為對(duì)照組,提取所有受試者外周血DNA。通過(guò)生物信息學(xué)方法從多個(gè)公開的生物學(xué)信息庫(kù)中在目前已報(bào)道的所有在AD腦內(nèi)差異表達(dá)的3’UTR mi RNAs的靶基因中篩選出在漢族人群中常見的AD易感基因GAB2,并用最終確定了3’UTR mi RNAs-185的特異性靶向序列中的一個(gè)常見的單核苷酸多態(tài)位點(diǎn)rs3740677。并利用多重高溫連接酶檢測(cè)反應(yīng)(i MLDR)技術(shù)進(jìn)行了相關(guān)基因分型。此外,我們還應(yīng)用等位基因特異性多重PCR(Multi-ARMS)技術(shù)進(jìn)行了APOE基因分型。最后我們應(yīng)用SPSS19.0軟件,采取t檢驗(yàn)、卡方檢驗(yàn)及Logistic回歸分析等方法對(duì)相關(guān)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,得到相關(guān)統(tǒng)計(jì)學(xué)檢驗(yàn)值:P值,OR值及其95%可信區(qū)間等,進(jìn)而判斷此SNP位點(diǎn)與北方漢族人群遲發(fā)性AD發(fā)病的可能關(guān)系。結(jié)果:GAB2 SNP rs3740677基因型顯示等位基因“T”為最小頻率等位基因。通過(guò)卡方檢驗(yàn),我們發(fā)現(xiàn)GAB2 SNP rs3740677的基因型與最小等位基因T在LOAD病例組與健康對(duì)照組間均存在顯著統(tǒng)計(jì)學(xué)差異(基因型P=0.024;等位基因P=0.008)。此外,作為GAB2 SNP rs3740677的預(yù)期風(fēng)險(xiǎn)等位基因T,我們的卡方檢驗(yàn)分析發(fā)現(xiàn)其可能對(duì)LOAD發(fā)病具有保護(hù)性作用(OR=0.833,95%CI=0.728-0.952)。通過(guò)對(duì)LOAD病例組以及健康對(duì)照組人群行進(jìn)一步的APOEε4攜帶與否分層,我們通過(guò)卡方檢驗(yàn)分析發(fā)現(xiàn):無(wú)論在APOEε4+(攜帶)還是APOEε4-(非攜帶)條件下均未發(fā)現(xiàn)GAB2 SNP rs3740677基因型與最小等位基因T分布在兩組間存在統(tǒng)計(jì)學(xué)差異(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,在經(jīng)過(guò)發(fā)病年齡或檢測(cè)年齡、性別、APOEε4攜帶狀態(tài)等因素調(diào)整后,我們通過(guò)邏輯學(xué)回歸分析檢測(cè)了三個(gè)基因型遺傳模態(tài)中的GAB2 SNP rs3740677基因型在兩組中的分布差異。最終結(jié)果顯示:在顯性遺傳模態(tài)以及疊加模態(tài)中發(fā)現(xiàn)了GAB2SNP rs3740677基因型分布的統(tǒng)計(jì)學(xué)差異,并且同樣呈現(xiàn)一種對(duì)AD發(fā)病的保護(hù)性作用。而在隱性遺傳模態(tài)中我們并未發(fā)現(xiàn)任何統(tǒng)計(jì)學(xué)意義(顯性遺傳模態(tài):OR=0.831,95%CI=0.702 0.983,P=0.031;疊加模態(tài):OR=0.855,95%CI=0.745 0.983,P=0.027;隱性遺傳模態(tài):P=0.252)。此外,我們更進(jìn)一步的檢測(cè)的三種模態(tài)中基因型分布與APOEε4狀態(tài)的可能交互作用。最終,均未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)意義。結(jié)論:我們的研究在北方漢族人群中首次證實(shí)了AD相關(guān)基因GAB2中一個(gè)3’UTR mi RNAs-185的特異性靶向序列中的常見SNPs rs3740677與LOAD發(fā)病的顯著關(guān)聯(lián)。而且SNPs rs3740677被進(jìn)一步提示是一種對(duì)LOAD發(fā)病具有保護(hù)性作用的影響因素。
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749.16

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