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

BACKGROUND: Late-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) a...

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Autores principales: Yuan, Lin, Wang, Leyuan, Du, Xizi, Qin, Ling, Yang, Ming, Zhou, Kai, Wu, Mengping, Yang, Yu, Zheng, Zhiyuan, Xiang, Yang, Qu, Xiangping, Liu, Huijun, Qin, Xiaoqun, Liu, Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726856/
https://www.ncbi.nlm.nih.gov/pubmed/33298101
http://dx.doi.org/10.1186/s12967-020-02643-y
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author Yuan, Lin
Wang, Leyuan
Du, Xizi
Qin, Ling
Yang, Ming
Zhou, Kai
Wu, Mengping
Yang, Yu
Zheng, Zhiyuan
Xiang, Yang
Qu, Xiangping
Liu, Huijun
Qin, Xiaoqun
Liu, Chi
author_facet Yuan, Lin
Wang, Leyuan
Du, Xizi
Qin, Ling
Yang, Ming
Zhou, Kai
Wu, Mengping
Yang, Yu
Zheng, Zhiyuan
Xiang, Yang
Qu, Xiangping
Liu, Huijun
Qin, Xiaoqun
Liu, Chi
author_sort Yuan, Lin
collection PubMed
description BACKGROUND: Late-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. METHODS: The 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. RESULTS: Compared 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. CONCLUSIONS: The 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.
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spelling pubmed-77268562020-12-10 The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma Yuan, Lin Wang, Leyuan Du, Xizi Qin, Ling Yang, Ming Zhou, Kai Wu, Mengping Yang, Yu Zheng, Zhiyuan Xiang, Yang Qu, Xiangping Liu, Huijun Qin, Xiaoqun Liu, Chi J Transl Med Research BACKGROUND: Late-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. METHODS: The 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. RESULTS: Compared 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. CONCLUSIONS: The 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. BioMed Central 2020-12-09 /pmc/articles/PMC7726856/ /pubmed/33298101 http://dx.doi.org/10.1186/s12967-020-02643-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yuan, Lin
Wang, Leyuan
Du, Xizi
Qin, Ling
Yang, Ming
Zhou, Kai
Wu, Mengping
Yang, Yu
Zheng, Zhiyuan
Xiang, Yang
Qu, Xiangping
Liu, Huijun
Qin, Xiaoqun
Liu, Chi
The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
title The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
title_full The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
title_fullStr The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
title_full_unstemmed The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
title_short The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
title_sort dna methylation of foxo3 and tp53 as a blood biomarker of late-onset asthma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726856/
https://www.ncbi.nlm.nih.gov/pubmed/33298101
http://dx.doi.org/10.1186/s12967-020-02643-y
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