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

doi:10.3969/j.issn.1006-7795.2021.03.018

首都医科大学学报 ›› 2021, Vol. 42 ›› Issue (3): 447-452.doi: 10.3969/j.issn.1006-7795.2021.03.018

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

郝淑文^1,2,3, 陈瑛^3,4,5, 丁晖^1,2,3, 赵春松^1,2,3,6, 梁阔^1,2,3,6, 薛金花^1,2,3,6, 蔡彦宁^1,2,3,6*

1.首都医科大学宣武医院神经生物学研究室,北京 100053;
2.教育部神经变性病重点实验室,北京 100053;
3.国家老年疾病临床医学研究中心, 北京 100053;
4.首都医科大学宣武医院神经内科,北京 100053;
5.浙江省台州市立医院神经内科, 浙江台州 318000;
6.首都医科大学宣武医院生物样本库,北京 100053

收稿日期:2020-04-28 出版日期:2021-06-21 发布日期:2021-06-16
通讯作者: *E-mail:yanningcai@hotmail.com
基金资助:
国家重点研发计划精准医学研究重点专项(2017YFC0909100)。

Methylation analysis of multiple genes in blood DNA of patients with Alzheimer's disease, mild cognitive impairment and subjective cognitive decline

Hao Shuwen^1,2,3, Chen Ying^3,4,5, Ding Hui^1,2,3, Zhao Chunsong^1,2,3,6, Liang Kuo^1,2,3,6, Xue Jinhua^1,2,3,6, Cai Yanning^1,2,3,6*

1. Department of Neurobiology,Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
2. Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, China;
3. National Clinical Research Center for Geriatric Disorders, Beijing 100053, China;
4. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
5. Department of Neurology, Zhejiang Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, China;
6. Department of Biobank, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2020-04-28 Online:2021-06-21 Published:2021-06-16
Contact: *E-mail:yanningcai@hotmail.com
Supported by:
National Key R&D Program of China (2017YFC0909100).

摘要/Abstract

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, ALOX5), CBFA2/RUNX1伴侣转录共抑制因子3(CBFA2/RUNX1 partner transcriptional co-repressor 3,CBFA2T3)和碱性螺旋-环-螺旋转录因子家族成员E23 (basic helix-loop-helix family member e23,BHLHE23)基因启动子的DNA甲基化水平。结果 FAAH、ALOX5、CBFA2T3、BHLHE23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。

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

Abstract: 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 thefatty acid amide hydrolase(FAAH), arachidonate 5-lipoxygenase(ALOX5), CBFA2/RUNX1 partner transcriptional co-repressor 3(CBFA2T3) and basic helix-loop-helix family member e23(BHLHE23)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 BHLHE23 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.

Key words: DNA methylation, pyrosequencing, Alzheimer's disease, amnestic mild cognitive impairment, subjective cognitive decline

中图分类号:

郝淑文, 陈瑛, 丁晖, 赵春松, 梁阔, 薛金花, 蔡彦宁. 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[J]. 首都医科大学学报, 2021, 42(3): 447-452.

Hao Shuwen, Chen Ying, Ding Hui, Zhao Chunsong, Liang Kuo, Xue Jinhua, Cai Yanning. Methylation analysis of multiple genes in blood DNA of patients with Alzheimer's disease, mild cognitive impairment and subjective cognitive decline[J]. Journal of Capital Medical University, 2021, 42(3): 447-452.

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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

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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