Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

Abstract We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray...

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Autores principales:	Yung-Che Chen, Ying-Huang Tsai, Chin-Chou Wang, Shih-Feng Liu, Ting-Wen Chen, Wen-Feng Fang, Chiu-Ping Lee, Po-Yuan Hsu, Tung-Ying Chao, Chao-Chien Wu, Yu-Feng Wei, Huang-Chih Chang, Chia-Cheng Tsen, Yu-Ping Chang, Meng-Chih Lin, Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1877691a9343459ba0123e3ee125f2bc
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spelling	oai:doaj.org-article:1877691a9343459ba0123e3ee125f2bc2021-12-02T13:19:21ZEpigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes10.1038/s41598-021-83185-12045-2322https://doaj.org/article/1877691a9343459ba0123e3ee125f2bc2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83185-1https://doaj.org/toc/2045-2322Abstract We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.Yung-Che ChenYing-Huang TsaiChin-Chou WangShih-Feng LiuTing-Wen ChenWen-Feng FangChiu-Ping LeePo-Yuan HsuTung-Ying ChaoChao-Chien WuYu-Feng WeiHuang-Chih ChangChia-Cheng TsenYu-Ping ChangMeng-Chih LinTaiwan Clinical Trial Consortium of Respiratory Disease (TCORE) groupNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yung-Che Chen Ying-Huang Tsai Chin-Chou Wang Shih-Feng Liu Ting-Wen Chen Wen-Feng Fang Chiu-Ping Lee Po-Yuan Hsu Tung-Ying Chao Chao-Chien Wu Yu-Feng Wei Huang-Chih Chang Chia-Cheng Tsen Yu-Ping Chang Meng-Chih Lin Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
description	Abstract We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.
format	article
author	Yung-Che Chen Ying-Huang Tsai Chin-Chou Wang Shih-Feng Liu Ting-Wen Chen Wen-Feng Fang Chiu-Ping Lee Po-Yuan Hsu Tung-Ying Chao Chao-Chien Wu Yu-Feng Wei Huang-Chih Chang Chia-Cheng Tsen Yu-Ping Chang Meng-Chih Lin Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group
author_facet	Yung-Che Chen Ying-Huang Tsai Chin-Chou Wang Shih-Feng Liu Ting-Wen Chen Wen-Feng Fang Chiu-Ping Lee Po-Yuan Hsu Tung-Ying Chao Chao-Chien Wu Yu-Feng Wei Huang-Chih Chang Chia-Cheng Tsen Yu-Ping Chang Meng-Chih Lin Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group
author_sort	Yung-Che Chen
title	Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
title_short	Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
title_full	Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
title_fullStr	Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
title_full_unstemmed	Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
title_sort	epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant dna methylations related to clinical phenotypes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1877691a9343459ba0123e3ee125f2bc
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Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

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