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生长因子颗粒蛋白前体和肿瘤坏死因子受体基因启动子区改变与阿尔茨海默病的相关性研究 被引量:1

The Correlation between the Changes in PGRN and TNFR Gene Promoters and Alzheimer's Disease
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摘要 目的:探讨生长因子颗粒蛋白前体(PGRN)、肿瘤坏死因子受体(TNFR)基因启动子区改变以及全基因组DNA甲基化与阿尔茨海默病的相关性。方法:收集阿尔茨海默病患者血液样本80例以及健康对照血液样本80例,PCR扩增PGRN和TNFR基因启动子区并进行测序,观察两组间的单核苷酸多态性位点是否有差异。同时,用甲基化特异性PCR法检测启动子区DNA甲基化情况以及用ELISA法检测全基因组DNA甲基化水平。结果:在TNFR基因启动子区域发现阿尔茨海默病和对照组之间在多态性位点rs4149570和rs4149569有显著性差异(P<0.001和P=0.033)。阿尔茨海默病患者全基因组甲基化水平为(0.79±0.29)%,显著低于对照组的(1.00±0.36)%(P<0.001)。结论:TNFR基因多态性位点rs4149570和rs4149569的变异可能与阿尔茨海默病相关,全基因组甲基化水平降低可能与阿尔茨海默病相关。 Objective: To investigate the correlation between the Alzheimer's disease (AD) and the changes in promoter regions of progranulin (FGRN) and tumor necrosis factor receptor (TNFR) and the whole genome DNA methylation status. Methods: Eighty blood specimen were collected from ALzheimer's disease patients and another eighty blood specimen were collected from healthy people. The promoter regions of PGRN and TNFR were amplified by Polymerase chain reaction (PCR) and were sequenced to detect the difference of the sequence variations (SNPs) in two groups. At the same time, DNA methylation levels in PGRN and TNFR promoter regions and in whole genome were detected with methlation specific PCR and ELISA respectively. Results: Significant differences were found in rs4149570 and rs4149569 located in promoter regions of TNFR in patients compared to control group (P 〈0.001 and P=0.033). The whole genome methylation level was (0,79± 0.29)% in AIzheimer's disease group and lower than those in control group (1.00± 0.36)% (F 〈 0.001). Conclusion: TNFR promoter gene rs4149570 and rs4149569 variants and the decrease of whole genome DNA methylation were related to AD.
出处 《现代生物医学进展》 CAS 2016年第28期5401-5404,共4页 Progress in Modern Biomedicine
基金 国家自然科学基金项目(81201334)
关键词 阿尔茨海默病 生长因子颗粒蛋白前体 肿瘤坏死因子受体 启动子区 甲基化 Alzheimer's disease (AD) Progranulin (PGRN) Tumor necrosis factor receptor (TNFR) Fromoter Methylation
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