Evidence map›Paper›PMID 33298101›Full record

ArticleJournal of translational medicine2020

The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma.

Lin Yuan, Leyuan Wang, Xizi Du, Ling Qin, Ming Yang, Kai Zhou, Mengping Wu, Yu Yang, Zhiyuan Zheng, Yang Xiang and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
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  4. Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoclastogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  9. Review
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  11. Newborn DNA methylation and asthma acquisition across adolescence and early adulthood.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Aberrant Methylation of Aging-Related Genes in Asthma.Frontiers in molecular biosciences · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 2 countries.

Lin YuanDepartment of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Leyuan WangDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Xizi DuDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Ling QinDepartment of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ming YangCentre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, Australia.
Kai ZhouDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Mengping WuDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Yu YangDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Zhiyuan ZhengDepartment of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yang XiangDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Xiangping QuDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Huijun LiuDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Xiaoqun QinDepartment of Physiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, 410078, Hunan, China.
Chi LiuDepartment of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China. liu.chi@csu.edu.cn.ORCID http://orcid.org/0000-0003-2872-9576
Central South University · CNHunter Medical Research Institute · AU

Funding

Fundamental Research Funds for the Central Universities of Central South University 2018zzts812Fundamental Research Funds for the Central Universities of Central South University 2018zzts813Fundamental Research Funds for the Central Universities of Central South University 2019zzts1008Fundamental Research Funds for the Central Universities of Central South University 2019zzts327Hunan Natural Science Foundation 2017JJ2402Hunan Natural Science Foundation 2019JJ50760National Natural Science Foundation of China 3167188National Natural Science Foundation of China 31900424National Natural Science Foundation of China 81570026National Natural Science Foundation of China 81670002National Natural Science Foundation of China 81970033National Natural Science Foundation of China 82070034open Foundation of Hunan College Innovation Program 20K142
6 · The paper itself

Abstract

backgroundLate-onset asthma (LOA) is beginning to account for an increasing proportion of asthma patients, which is often underdiagnosed in the elderly. Studies on the possible relations between aging-related genes and LOA contribute to the diagnosis and treatment of LOA. Forkhead Box O3 (FOXO3) and TP53 are two classic aging-related genes. DNA methylation varies greatly with age which may play an important role in the pathogenesis of LOA. We supposed that the differentially methylated sites of FOXO3 and TP53 associated with clinical phenotypes of LOA may be useful biomarkers for the early screening of LOA.

methodsThe mRNA expression and DNA methylation of FOXO3 and TP53 in peripheral blood of 43 LOA patients (15 mild LOA, 15 moderate LOA and 13 severe LOA) and 60 healthy controls (HCs) were determined. The association of methylated sites with age was assessed by Cox regression to control the potential confounders. Then, the correlation between differentially methylated sites (DMSs; p-value < 0.05) and clinical lung function in LOA patients was evaluated. Next, candidate DMSs combining with age were evaluated to predict LOA by receiver operating characteristic (ROC) analysis and principal components analysis (PCA). Finally, HDM-stressed asthma model was constructed, and DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-AZA) were used to determine the regulation of DNA methylation on the expression of FOXO3 and TP53.

resultsCompared with HCs, the mRNA expression and DNA methylation of FOXO3 and TP53 vary significantly in LOA patients. Besides, 8 DMSs from LOA patients were identified. Two of the DMSs, chr6:108882977 (FOXO3) and chr17:7591672 (TP53), were associated with the severity of LOA. The combination of the two DMSs and age could predict LOA with high accuracy (AUC values = 0.924). In HDM-stressed asthma model, DNA demethylation increased the expression of FOXO3 and P53.

conclusionsThe mRNA expression of FOXO3 and TP53 varies significantly in peripheral blood of LOA patients, which may be due to the regulation of DNA methylation. FOXO3 and TP53 methylation is a suitable blood biomarker to predict LOA, which may be useful targets for the risk diagnosis and clinical management of LOA.

Indexed as

AsthmaDNA MethylationAgedBiomarkersForkhead Box Protein O3HumansLungPhenotypeTumor Suppressor Protein p53BiomarkersForkhead Box Protein O3FOXO3 protein, humanTP53 protein, humanTumor Suppressor Protein p53AgingDNA methylationFOXO3Late-onset asthmaTP53

Identifiers

PMID33298101
PMCPMC7726856
OpenAlexW3112052973

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.