Variable DNA methylation of aging-related genes is associated with male COPD.
Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Aging
/ blood
Case-Control Studies
CpG Islands
DNA Methylation
Databases, Genetic
Female
Forced Expiratory Volume
Forkhead Transcription Factors
/ genetics
Genetic Predisposition to Disease
Humans
Lung
/ physiopathology
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive
/ blood
Risk Assessment
Risk Factors
Severity of Illness Index
Sex Factors
Transcriptome
Vital Capacity
Young Adult
Aging
Aging-related genes
COPD
DNA methylation
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
04 Nov 2019
04 Nov 2019
Historique:
received:
15
04
2019
accepted:
15
10
2019
entrez:
6
11
2019
pubmed:
7
11
2019
medline:
28
4
2020
Statut:
epublish
Résumé
Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown. Firstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients. Of the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking. These results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.
Sections du résumé
BACKGROUND
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown.
METHODS
METHODS
Firstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients.
RESULTS
RESULTS
Of the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking.
CONCLUSION
CONCLUSIONS
These results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.
Identifiants
pubmed: 31684967
doi: 10.1186/s12931-019-1215-7
pii: 10.1186/s12931-019-1215-7
pmc: PMC6829949
doi:
Substances chimiques
FOXP3 protein, human
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
243Subventions
Organisme : National Natural Science Foundation of China-Yunnan Joint Fund
ID : #81570026, #81670002 and #3167188
Organisme : National Natural Science Foundation of China-Yunnan Joint Fund
ID : #81570026, #81670002 and #3167188
Organisme : Natural Science Foundation of Hunan Province
ID : #2017JJ2402
Organisme : open Foundation of Hunan College Innovation Program
ID : #16K097, #14K109
Organisme : Young Elite Scientists Sponsors hip Program
ID : #2015QNRC001
Organisme : Fundamental Research Funds for Central Universities of the Central South University
ID : #2018zzts812
Organisme : Fundamental Research Funds for Central Universities of the Central South University
ID : #2018zzts813
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