中国汉族人群MTHFD1L基因多态性与阿尔茨海默病的关联性研究

发布时间：2018-03-16 09:52

本文选题：阿尔茨海默病　切入点：亚甲基四氢叶酸脱氧酶1-蛋白基因　出处：《青岛大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的本研究旨在探讨亚甲基四氢叶酸脱氢酶1-蛋白(MTHFD1L)基因单核甘酸多态性与迟发性阿尔茨海默病(Late-onset Alzheimer's disease, LOAD)易感性的关系。方法采用病例-对照研究方法,选取582例LOAD患者和607例年龄和性别相匹配的健康对照作为研究对象。根据最近报道的一项LOAD全基因组关联研究,选取2个的SNPs位点(rs11754661, rs2073067)利用聚合酶链式反应—连接酶检测反应(PCR-LDR)技术进行基因分型,并进行关联分析。应用等位基因特异性多重PCR (Multi-ARMS)技术进行APOE基因分型。结果MTHFD1L基因rs11754661及rs2073067多态性位点与LOAD的易感性相关联,携带rs11754661最小等位基因可增加LOAD的发病风险(OR=1.727,p=0.016),对于rs2073067位点,仅在按ApoE ε4等位基因分组后,在APOE ε4等位基因携带者组中,携带rs2073067最小等位基因可降低LOAD的发病风险(OR=0.400,P＜0.001)。多因素回归分析显示,在校正年龄、姓别及APOE ε4携带状态等因素后,在显性模型中rs11754661多态位点仍与LOAD的发病风险升高显著相关(OR=1.627,95%CI=1.016-2.604, P=0.043)。 rs11754661和rs2073067在同一个连锁不平衡区域,它们所构建的单倍体型AC与LOAD发病风险的升高显著相关(OR=1.730,95%CI=1.105-2.709, P=0.015). 结论MTHFD1L基因为汉族人群LOAD的易感基因,其遗传多态性与汉族人LOAD的发病相关联,进一步的深入研究MTHFD1L基因在LOAD的发生过程中的作用机制,有望为AD治疗开辟一条新的治疗道路。
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16

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