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

doi:10.3969/j.issn.1006-7795.2021.03.018

Journal of Capital Medical University ›› 2021, Vol. 42 ›› Issue (3): 447-452.doi: 10.3969/j.issn.1006-7795.2021.03.018

• Clinical Research • Previous Articles Next Articles

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).

Abstract

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

CLC Number:

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.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2021.03.018

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2021/V42/I3/447

References

[1] Scheltens P, Blennow K, Breteler M M,et al.Alzheimer's disease[J].Lancet,2016,388(10043):505-517.
[2] Petersen R C, Doody R, Kurz A, et al.Current concepts in mild cognitive impairment[J].Arch Neurol,2001,58(12):1985-1992.
[3] Langa K M,Levine D A.The diagnosis and management of mild cognitive impairment:a clinical review[J].JAMA,2014,312(23):2551-2561.
[4] Jessen F, Amariglio R E, van Boxtel M, et al.A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease[J].Alzheimers Dement,2014,10(6):844-852.
[5] Di Francesco A, Arosio B, Falconi A, et al.Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells[J].Brain Behav Immun,2015,45:139-144.
[6] Kobayashi N, Shinagawa S, Nagata T, et al.Development of biomarkers based on DNA methylation in the NCAPH2/LMF2 promoter region for diagnosis of alzheimer's disease and amnesic mild cognitive impairment[J].PLoS One,2016,11(1):e0146449.
[7] D'Addario C, Di Francesco A, Arosio B, et al.Epigenetic regulation of fatty acid amide hydrolase in Alzheimer disease[J].PLoS One,2012,7(6):e39186.
[8] Di Francesco A, Arosio B, Gussago C, et al.Involvement of 5-lipoxygenase in Alzheimer's disease:a role for DNA methylation[J].J Alzheimers Dis,2013,37(1):3-8.
[9] Lunnon K, Smith R G, Cooper I, et al.Bloodmethylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus[J].Neurobiol Aging,2015,36(3):1600.e1-4.
[10] Chang L, Wang Y, Ji H, et al.Elevation of peripheral BDNF promoter methylation links to the risk of Alzheimer's disease[J].PLoS One,2014,9(11):e110773.
[11] Ji H, Wang Y, Liu G, et al.Elevated OPRD1 promoter methylation in Alzheimer's disease patients[J].PLoS One,2017,12(3):e0172335.
[12] Ji H, Wang Y, Liu G, et al.OPRK1 promoter hypermethylation increases the risk of Alzheimer's disease[J].Neurosci Lett,2015,606:24-29.
[13] Jack C R Jr, Albert M S, Knopman D S, et al.Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease[J].Alzheimers Dement,2011,7(3):257-262.
[14] Petersen R C.Mild cognitive impairment as a diagnostic entity[J].J Intern Med,2004,256(3):183-194.
[15] Lin Q, Ding H, Zheng Z, et al.Promoter methylation analysis of seven clock genes in Parkinson's disease[J].Neurosci Lett,2012,507(2):147-150.
[16] Benito C, Núñez E, Pazos M R, et al.The endocannabinoid system and Alzheimer's disease[J].Mol Neurobiol,2007,36(1):75-81.
[17] Phillis J W, Horrocks L A, Farooqui A A.Cyclooxygenases, lipoxygenases, and epoxygenases in CNS:their role and involvement in neurological disorders[J].Brain Res Rev,2006,52(2):201-243.
[18] Manev H, Chen H, Dzitoyeva S, et al.Cyclooxygenases and 5-lipoxygenase in Alzheimer's disease[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(2):315-319.
[19] Asada K, Watanabe N, Nakamura Y, et al.Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas[J].Jpn J Clin Oncol,2013,43(6):641-645.
[20] Chambers J C, Loh M, Lehne B, et al.Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes:a nested case-control study[J].Lancet Diabetes Endocrinol,2015,3(7):526-534.
[21] Koestler D C, Christensen B, Karagas M R, et al.Blood-based profiles of DNA methylation predict the underlying distribution of cell types:a validation analysis[J].Epigenetics, 2013,8(8):816-826.
[22] Kinoshita M, Numata S, Tajima A, et al.Aberrant DNA methylation of blood in schizophrenia by adjusting for estimated cellular proportions[J].Neuromolecular Med,2014,16(4):697-703.
[23] Shinohara M, Sato N.Bidirectional interactions between diabetes and Alzheimer's disease[J].Neurochem Int, 2017,108:296-302.

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

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 7

Recommended Articles

Metrics

Comments

[1]	Zhao Xiaoxiao, Yu Qiuhong, Ji Jianghuai, Wang Shijia, Wang Rendong, Li Dongguo. Identification of protein-coding genes regulated by differential DNA methylation enhancer regions in glioblastoma [J]. Journal of Capital Medical University, 2022, 43(1): 113-119.
[2]	Ji Jianghuai, Zhao Xiaoxiao, Li Qianpeng, An Yi, Zhao Lei, Li Dongguo. Identification of protein-coding genes regulated by aberrant methylation in glioblastoma [J]. Journal of Capital Medical University, 2021, 42(1): 71-76.
[3]	Yang Zhaofei, Wang Yong, Yang Jian, Wang Xuan, Wang Xiaomin. L-DOPA regulates MAO-B transcription through DNA methylation in SH-SY5Y cells [J]. Journal of Capital Medical University, 2015, 36(5): 734-739.
[4]	Wang Qinggang, Meng Ying, Zhu Shengtao, Shi Haiyun, Zhang Shutian. Effect of promoter methylation on lower expressed cyclooxygenase-2 esophageal squamous cell carcinoma xenograft [J]. Journal of Capital Medical University, 2014, 35(6): 798-804.
[5]	Wang Danhui, Cai Yanning, Zhang Yanli, Gao Jie, Yang Caixia. Establishment of pyrosequencing method to detect isocitrate dehydrogenase 1 mutations [J]. Journal of Capital Medical University, 2014, 35(2): 219-224.
[6]	WANG Jian-long;LI Hai-tao;SU Pi-xiong;GU Song;LIU Yan;ZHANG Xi-tao;YAN Jun;AN Xiang-gang;GAO Jie;XIN Yue;CAI Jun. Altered whole genomic methylation in chronic heart failure patients [J]. Journal of Capital Medical University, 2012, 33(4): 427-431.
[7]	ZUO Xiao-hong;LIU Shu;LIN Qing-ling;LI Ning;CHEN Biao;CAI Yan-ning. Circadian E-boxes and surrounding CpG islands are free from methylation throughout the day [J]. Journal of Capital Medical University, 2011, 32(6): 781-786.