老年2型糖尿病病人心血管病死亡相关外周血全基因组DNA甲基化的研究

doi:10.3969/j.issn.1003-9198.2022.05.009

Abstract

Abstract: Objective A genome-wide DNA methylation microarray technique was used to explore the aberrantly methylated sites in the elderly patients with type 2 diabetes mellitus(T2DM) suffering from cardiovascular disease-induced death. Methods The present study was conducted using the data from the Staged Diabetes Targeting Management (SDTM)study. The propensity score method was used to match the control, and the calipers value was set to 0.02. Twelve elderly patients with T2DM who died of cardiovascular disease until October 2017 were selected as case group. Twelve elderly patients with T2DM who survived in the same period were selected as the control group. Whole genome methylation level in periphral blood was detected by Illumina Methylation BeadChip. Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway analysis were performed using the DAVID database. Results A total of 303 CpG sites with statistically significant differences were found. GO function analysis showed that methylation variation positions were involved in such biological process as:(1) Nervous system development, cell adhesion, glucose homeostasis and positive regulation of dendrite development; (2)Cellular component such as integral component of plasma membrane, dendrite and perinuclear region of cytoplasm; (3) Molecular function such as calcium ion binding and sequence-specific DNA binding. KEGG signaling pathway analysis found that methylation variation positions were involved in cyclic adenosine monophosphate(cAMP) signaling pathway and inflammatory mediator regulation of transient receptor potential(TRP) channels. Conclusions DNA methylation modification may be involved in the pathogenesis of the elderly patients with T2DM who die of cardiovascular disease.

Key words: aged, cardiovascular disease-induced death, type 2 diabetes mellitus, 850K methylation chip, methylation markers

CLC Number:

R 587.1

FAN Yao, WANG Qiang, TANG Ji-hong, LOU Qing-lin, TANG Wei, GU Liu-bao. Analysis of genomic DNA methylation of peripheral blood in elderly patients with type 2 diabetes mellitus suffering form cardiovascular disease-induced death[J]. Practical Geriatrics, 2022, 36(5): 468-472.

References

[1] MAHAJAN A, TALIUN D, THURNER M, et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps[J]. Nat Genet, 2018,50(11):1505-1513.
[2] MORRIS A P, VOIGHT B F, TESLOVICH T M, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes[J]. Nat Genet, 2012,44(9):981-990.
[3] MAHAJAN A, GO M J, Zhang W, et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility[J]. Nat Genet, 2014,46(3):234-244.
[4] BERNSTEIN B E, MEISSNER A, LANDER E S. The mammalian epigenome[J]. Cell, 2007,128(4):669-681.
[5] GREENBERG M, BOURC′HIS D B. The diverse roles of DNA methylation in mammalian development and disease[J]. Nat Rev Mol Cell Biol, 2019,20(10):590-607.
[6] EHRLICH M, LACEY M. DNA methylation and differentiation: silencing, upregulation and modulation of gene expression[J]. Epigenomics, 2013,5(5):553-568.
[7] 欧阳晓俊, 莫永珍, 卞茸文,等. 分阶段糖尿病达标管理改善2型糖尿病患者糖化血红蛋白水平的自身对照及优化治疗方案的观察[J]. 中国糖尿病杂志,2013,21(8):713-716.
[8] MAZZONE T. Intensive glucose lowering and cardiovascular disease prevention in diabetes: reconciling the recent clinical trial data[J]. Circulation, 2010,122(21):2201-2211.
[9] 赵丹, 王沛坚, 周鹏. TRPA1/TRPV1在心血管疾病中的作用[J]. 成都医学院学报,2019,14(6):819-822.
[10] HUANG W, RUBINSTEIN J, PRIETO A R, et al. Transient receptor potential vanilloid gene deletion exacerbates inflammation and atypical cardiac remodeling after myocardial infarction[J]. Hypertension, 2009,53(2):243-250.
[11] 赵向凤, 邓文涛, 储小飞,等. TRPV1基因多态性与2型糖尿病遗传易感性及术中不良心血管事件的关系[J]. 中华麻醉学杂志,2020,40(5):557-560.
[12] XIAO Y F, NIKOLSKAYA A, JAYE D A, et al. Glucagon-like peptide-1 enhances cardiac L-type Ca2+ currents via activation of the cAMP-dependent protein kinase A pathway[J]. Cardiovasc Diabetol, 2011,10:6.
[13] BAGGIO L L, DRUCKER D J. Biology of incretins: GLP-1 and GIP[J]. Gastroenterology, 2007,132(6):2131-2157.
[14] LEE C H, YAN B, YOO K Y, et al. Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia[J]. J Neurosci Res, 2011,89(7):1103-1113.
[15] FLAMEZ D, GILON P, MOENS K, et al. Altered cAMP and Ca²⁺ signaling in mouse pancreatic islets with glucagon-like peptide-1 receptor null phenotype[J]. Diabetes, 1999,48(10):1979-1986.
[16] DOZIER K C, CURETON E L, KWAN R O, et al. Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation[J]. Peptides, 2009,30(9):1735-1741.
[17] LIU L, LIU J, WONG W T, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism[J]. Hypertension, 2012,60(3):833-841.
[18] 季慧慧, 郑中华, 邬博逸,等. 女性2型糖尿病患者外周血全基因组DNA甲基化的研究[J]. 中国糖尿病杂志,2020,28(8):568-575.
[19] 成淑英, 李楠, 张利红,等. 血管细胞黏附分子-1与2型糖尿病大血管病变关系研究[J]. 陕西医学杂志,2017,46(7):902-904.
[20] URRY D W. Neutral sites for calcium ion binding to elastin and collagen: a charge neutralization theory for calcification and its relationship to atherosclerosis[J]. Proc Natl Acad Sci U S A, 1971,68(4):810-814.
[21] LIANG W, SUN F, ZhAO Y, et al. Identification of susceptibility modules and genes for cardiovascular disease in diabetic patients using WGCNA analysis[J]. J Diabetes Res, 2020,2020:4178639.

Analysis of genomic DNA methylation of peripheral blood in elderly patients with type 2 diabetes mellitus suffering form cardiovascular disease-induced death

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Recommended 10

[1]	LI Jiang, QIU Yan, WANG Ting, WANG Dan, YU Yifan, PU Lingli, BU Ling. Correlation between preoperative SII/ALB and clinicopathologic features in elderly patients with lung adenocarcinoma [J]. Practical Geriatrics, 2024, 38(9): 893-896.
[2]	GAO Yuan, CHEN Hua, CHEN Ke, HUANG Wenlong. Relationship of bone mineral density and fracture risk with type 2 diabetes mellitus-related factors in elderly patients [J]. Practical Geriatrics, 2024, 38(9): 911-915.
[3]	DAI Jing, CUI Yan. Correlation between glycosylated hemoglobin variability and cognitive dysfunction in elderly patients with type 2 diabetes mellitus [J]. Practical Geriatrics, 2024, 38(9): 931-935.
[4]	ZHENG Hong, QI Zhenbo, XU Peng, XU Jie, YU Xinyu, ZANG Yanan, ZHANG Zhaoyan. Effects of hypnotics on cognition function and daytime sleepiness in the elderly [J]. Practical Geriatrics, 2024, 38(9): 936-939.
[5]	ZHANG Xingxing, ZHANG Haiyang, HE Xiaojing, LU Xiang. Investigation on the relationship between different physical indexes and the risk of diabetes mellitus in the elderly [J]. Practical Geriatrics, 2024, 38(9): 940-943.
[6]	NI Hongyan, CHEN Yun, ZHANG Qibing, MA Yiming, XIE Chenglan. Effects of electroacupuncture on cognitive function and inflammatory factors in elderly patients undergoing lower limb orthopedic surgery during the perioperative period [J]. Practical Geriatrics, 2024, 38(9): 944-947.
[7]	LI Xiaomin, LI Xiaolin, LI Jie, WU Lei, HAO Ranran. Efficiency influencing factors of transanal double-balloon enteroscopy in elderly patients [J]. Practical Geriatrics, 2024, 38(9): 958-961.
[8]	CAI Huicui, CHEN Yan, WANG Yan, YE Jinjun, ZHU Yuying. Effects of diversified health education model with simple respiratory function exercise on cancer-related fatigue and compliance behavior in elderly patients with lung cancer receiving radiotherapy [J]. Practical Geriatrics, 2024, 38(9): 968-972.
[9]	WANG Xiaojiao, WANG Ning, CUI Hong, YE Tong, WANG Xiaoming. Influence of exercise rehabilitation in elderly patients with mild to moderate chronic heart failure [J]. Practical Geriatrics, 2024, 38(8): 775-778.
[10]	SHEN Chenjun, WANG Xiaoqing, TANG Degang, NING Ping. Correlation between standardized uric acid and renal function in elderly patients with chronic kidney disease aged 90 and over [J]. Practical Geriatrics, 2024, 38(8): 779-782.
[11]	HAO Shijie, ZOU Jianpeng, WEI Chen, LIU Qingjiang. Effect of comprehensive respiratory training on hypokinetic dysarthria in elderly patients with Parkinson’s disease [J]. Practical Geriatrics, 2024, 38(8): 783-787.
[12]	XIANG Chao, LUO Caidong. Analysis of the diagnostic value of T wave change of avL lead for the degree of coronary artery stenosis in elderly patients with coronary heart disease [J]. Practical Geriatrics, 2024, 38(8): 788-791.
[13]	LI Huiying, CAI Lili, ZHU Qiwei. Predictive value of plasma N-terminal pro-brain natriuretic peptide for prognosis in patients aged ≥80 years old with left ventricular hypertrophy [J]. Practical Geriatrics, 2024, 38(8): 797-801.
[14]	WANG Xinping, XIE Baimei, WEI Guo, YE Xiaoli, ZHAO Yayun, TAN Xiaotian. Expression levels and clinical significance of serum S100A9 and sCD163 in elderly patients with idiopathic interstitial pneumonia [J]. Practical Geriatrics, 2024, 38(8): 802-807.
[15]	LIU Meijuan, WANG Ning, WANG Dong, LU Fangzhou, LIU Juan. Effect of low-dose lidocaine combined with propofol on motor evoked potential in elderly patients undergoing intracranial tumor resection [J]. Practical Geriatrics, 2024, 38(8): 808-811.