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阿尔茨海默病、轻度认知功能障碍及主观认知下降患者血液DNA中多个基因的甲基化分析 被引量:4

Methylation analysis of multiple genes in blood DNA of patients with Alzheimer s disease, mild cognitive impairment and subjective cognitive decline
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摘要 目的检验阿尔茨海默病(Alzheimer s disease,AD)、遗忘型轻度认知功能障碍(amnestic mild cognitive impairment,aMCI)、主观认知下降(subjective cognitive decline,SCD)患者和正常对照组多个基因的启动子DNA甲基化水平,并探讨是否可以作为SCD患者诊断的生物标志物。方法使用亚硫酸氢盐焦磷酸测序检验31例AD患者,41例aMCI患者,57例SCD患者和57例健康对照外周血白细胞中脂肪酸酰胺水解酶(fatty acid amide hydrolase,FAAH),花生四烯酸5-脂氧合酶(arachidonate 5-lipoxygenase,ALOX 5),CBFA2/RUNX1伴侣转录共抑制因子3(CBFA2/RUNX1 partner transcriptional co-repressor 3,CBFA2T 3)和碱性螺旋-环-螺旋转录因子家族成员E23(basic helix-loop-helix family member e23,BHLHE 23)基因启动子的DNA甲基化水平。结果FAAH、ALOX 5、CBFA 2 T 3、BHLHE 23基因在AD、aMCI、SCD患者外周血中的DNA甲基化水平与对照组相比,差异均无统计学意义(P>0.05)。根据性别及载脂蛋白E(apolipoprotein E,APOE)基因型分层分析,各组间外周血中的DNA甲基化水平差异亦无统计学意义(P>0.05)。结论4个基因的异甲基化水平与AD、aMCI、SCD无关联。 Objective To examine DNA methylation levels in the promoters of multiple genes in patients with Alzheimer s disease(AD),amnestic mild cognitive impairment(aMCI),subjective cognitive decline(SCD)and normal controls(NC)and to examine whether DNA methylation in these genes could serve as a diagnostic biomarker for SCD.Methods Using bisulfite pyrosequencing to examine DNA methylation levels in the fatty acid amide hydrolase(FAAH),arachidonate 5-lipoxygenase(ALOX 5),CBFA2/RUNX1 partner transcriptional co-repressor 3(CBFA2T 3)and basic helix-loop-helix family member e23(BHLHE 23)promoters in peripheral blood leukocytes of patients with AD(n=31),aMCI(n=41),SCD(n=57)and normal controls(n=57).Results The DNA methylation levels of FAAH,ALOX5,CBFA2T3 and BHLHE 23 genes were not statistically different in the peripheral blood of patients with AD,aMCI or SCD,compared with normal controls(P>0.05).According to the stratified analysis of gender and apolipoprotein E(APOE)genotype,there was no statistically significant difference in the DNA methylation levels in the peripheral blood among the groups(P>0.05).Conclusion The DNA methylation levels of the four genes weren t associated with AD,aMCI or SCD.
作者 郝淑文 陈瑛 丁晖 赵春松 梁阔 薛金花 蔡彦宁 Hao Shuwen;Chen Ying;Ding Hui;Zhao Chunsong;Liang Kuo;Xue Jinhua;Cai Yanning(Department of Neurobiology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Key Laboratory for Neurodegenerative Diseases of the Ministry of Education,Beijing 100053,China;National Clinical Research Center for Geriatric Disorders,Beijing 100053,China;Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Neurology,Zhejiang Taizhou Municipal Hospital,Taizhou 318000,Zhejiang Province,China;Department of Biobank,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)
出处 《首都医科大学学报》 CAS 北大核心 2021年第3期447-452,共6页 Journal of Capital Medical University
基金 国家重点研发计划精准医学研究重点专项(2017YFC0909100)。
关键词 DNA甲基化 焦磷酸测序 阿尔茨海默病 遗忘型轻度认知功能障碍 主观认知下降 DNA methylation pyrosequencing Alzheimer s disease amnestic mild cognitive impairment subjective cognitive decline
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