本文選題：阿爾茨海默病　切入點：亞甲基四氫葉酸脫氧酶1-蛋白基因　出處：《青島大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：目的本研究旨在探討亞甲基四氫葉酸脫氫酶1-蛋白(MTHFD1L)基因單核甘酸多態(tài)性與遲發(fā)性阿爾茨海默病(Late-onset Alzheimer's disease, LOAD)易感性的關(guān)系。 方法采用病例-對照研究方法,選取582例LOAD患者和607例年齡和性別相匹配的健康對照作為研究對象。根據(jù)最近報道的一項LOAD全基因組關(guān)聯(lián)研究,選取2個的SNPs位點(rs11754661, rs2073067)利用聚合酶鏈?zhǔn)椒磻?yīng)—連接酶檢測反應(yīng)(PCR-LDR)技術(shù)進(jìn)行基因分型,并進(jìn)行關(guān)聯(lián)分析。應(yīng)用等位基因特異性多重PCR (Multi-ARMS)技術(shù)進(jìn)行APOE基因分型。 結(jié)果MTHFD1L基因rs11754661及rs2073067多態(tài)性位點與LOAD的易感性相關(guān)聯(lián),攜帶rs11754661最小等位基因可增加LOAD的發(fā)病風(fēng)險(OR=1.727,p=0.016),對于rs2073067位點,僅在按ApoE ε4等位基因分組后,在APOE ε4等位基因攜帶者組中,攜帶rs2073067最小等位基因可降低LOAD的發(fā)病風(fēng)險(OR=0.400,P＜0.001)。多因素回歸分析顯示,在校正年齡、姓別及APOE ε4攜帶狀態(tài)等因素后,在顯性模型中rs11754661多態(tài)位點仍與LOAD的發(fā)病風(fēng)險升高顯著相關(guān)(OR=1.627,95%CI=1.016-2.604, P=0.043)。 rs11754661和rs2073067在同一個連鎖不平衡區(qū)域,它們所構(gòu)建的單倍體型AC與LOAD發(fā)病風(fēng)險的升高顯著相關(guān)(OR=1.730,95%CI=1.105-2.709, P=0.015). 結(jié)論MTHFD1L基因為漢族人群LOAD的易感基因,其遺傳多態(tài)性與漢族人LOAD的發(fā)病相關(guān)聯(lián),進(jìn)一步的深入研究MTHFD1L基因在LOAD的發(fā)生過程中的作用機制,有望為AD治療開辟一條新的治療道路。
[Abstract]:Objective to investigate the relationship between mononuclear glycosylated polymorphism of methylene tetrahydrofolate dehydrogenase (MTHFD1L) gene and susceptibility to Late-onset Alzheimer's disease (load) in patients with delayed Alzheimer's disease (AD). Methods A case-control study was conducted in 582 patients with LOAD and 607 age-matched healthy controls. Two SNPs loci (rs11754661, rs2073067) were selected for genotyping by polymerase chain reaction-ligase assay (PCR-LDR) and association analysis. Allele-specific multiplex PCR was used for APOE genotyping. Results rs11754661 and rs2073067 polymorphisms of MTHFD1L gene were associated with susceptibility to LOAD. Carrying the minimum rs11754661 allele could increase the risk of LOAD. For rs2073067 loci, only ApoE 蔚 4 alleles were grouped into APOE 蔚 4 alleles. Carrying the minimum allele of rs2073067 could reduce the risk of LOAD (P < 0.001). Multivariate regression analysis showed that after adjusting for age, surname and APOE 蔚 4 carrying status, and so on, In the dominant model, the polymorphic loci of rs11754661 were still significantly correlated with the increased risk of LOAD. Rs11754661 and rs2073067 were still in the same linkage disequilibrium region. The haploid type AC constructed by them was significantly correlated with the increased risk of the occurrence of LOAD (1.73095CI1.105-2.709, P0.015). Conclusion MTHFD1L gene is the susceptible gene of LOAD in Han population, and its genetic polymorphism is associated with the pathogenesis of LOAD in Han nationality. The role of MTHFD1L gene in the pathogenesis of LOAD is further studied. It is expected to open up a new treatment path for AD.
【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】：2013
【分類號】：R749.16

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