Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
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...
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2021
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ftnhri:oai:ir.nhri.org.tw:3990099045/13364 2023-07-02T03:32:05+02:00 Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes Chen, YC;Tsai, YH;Wang, CC;Liu, SF;Chen, TW;Fang, WF;Lee, CP;Hsu, PY;Chao, TY;Wu, CC;Wei, YF;Chang, HC;Tsen, CC;Chang, YP;Lin, MC;Yu, CJ;Wang, HC;Chiang, CH;Perng, DW;Cheng, SL;Hsu, JY;Hsu, WH;Hsiue, TR;Lin, HI;Wang, CY;Chang, YC;Chen, CM;Lin, CS;Chen, L;Chong, IW Taiwan Clinical Trial Consortium of Respiratory Disease Group Institute of Population Health Sciences 2021-03-03 4845534 bytes application/pdf http://ir.nhri.org.tw/handle/3990099045/13364 http://ir.nhri.org.tw/bitstream/3990099045/13364/1/SCP85102052319.pdf en-US eng NATURE PUBLISHING GROUP Scientific Reports. 2021 Mar 3;11:Article number 5022. 2045-2322 10.1038/s41598-021-83185-1 http://ir.nhri.org.tw/handle/3990099045/13364 http://ir.nhri.org.tw/bitstream/3990099045/13364/1/SCP85102052319.pdf Article 2021 ftnhri 2023-06-13T16:12:47Z 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. Article in Journal/Newspaper DML National Health Research Institutes (NHRI): Institutional Repository |
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National Health Research Institutes (NHRI): Institutional Repository |
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English |
description |
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. |
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Institute of Population Health Sciences |
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Article in Journal/Newspaper |
author |
Chen, YC;Tsai, YH;Wang, CC;Liu, SF;Chen, TW;Fang, WF;Lee, CP;Hsu, PY;Chao, TY;Wu, CC;Wei, YF;Chang, HC;Tsen, CC;Chang, YP;Lin, MC;Yu, CJ;Wang, HC;Chiang, CH;Perng, DW;Cheng, SL;Hsu, JY;Hsu, WH;Hsiue, TR;Lin, HI;Wang, CY;Chang, YC;Chen, CM;Lin, CS;Chen, L;Chong, IW Taiwan Clinical Trial Consortium of Respiratory Disease Group |
spellingShingle |
Chen, YC;Tsai, YH;Wang, CC;Liu, SF;Chen, TW;Fang, WF;Lee, CP;Hsu, PY;Chao, TY;Wu, CC;Wei, YF;Chang, HC;Tsen, CC;Chang, YP;Lin, MC;Yu, CJ;Wang, HC;Chiang, CH;Perng, DW;Cheng, SL;Hsu, JY;Hsu, WH;Hsiue, TR;Lin, HI;Wang, CY;Chang, YC;Chen, CM;Lin, CS;Chen, L;Chong, IW Taiwan Clinical Trial Consortium of Respiratory Disease Group Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes |
author_facet |
Chen, YC;Tsai, YH;Wang, CC;Liu, SF;Chen, TW;Fang, WF;Lee, CP;Hsu, PY;Chao, TY;Wu, CC;Wei, YF;Chang, HC;Tsen, CC;Chang, YP;Lin, MC;Yu, CJ;Wang, HC;Chiang, CH;Perng, DW;Cheng, SL;Hsu, JY;Hsu, WH;Hsiue, TR;Lin, HI;Wang, CY;Chang, YC;Chen, CM;Lin, CS;Chen, L;Chong, IW Taiwan Clinical Trial Consortium of Respiratory Disease Group |
author_sort |
Chen, YC;Tsai, YH;Wang, CC;Liu, SF;Chen, TW;Fang, WF;Lee, CP;Hsu, PY;Chao, TY;Wu, CC;Wei, YF;Chang, HC;Tsen, CC;Chang, YP;Lin, MC;Yu, CJ;Wang, HC;Chiang, CH;Perng, DW;Cheng, SL;Hsu, JY;Hsu, WH;Hsiue, TR;Lin, HI;Wang, CY;Chang, YC;Chen, CM;Lin, CS;Chen, L;Chong, IW |
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 PUBLISHING GROUP |
publishDate |
2021 |
url |
http://ir.nhri.org.tw/handle/3990099045/13364 http://ir.nhri.org.tw/bitstream/3990099045/13364/1/SCP85102052319.pdf |
genre |
DML |
genre_facet |
DML |
op_relation |
Scientific Reports. 2021 Mar 3;11:Article number 5022. 2045-2322 10.1038/s41598-021-83185-1 http://ir.nhri.org.tw/handle/3990099045/13364 http://ir.nhri.org.tw/bitstream/3990099045/13364/1/SCP85102052319.pdf |
_version_ |
1770271571808616448 |