Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes
We hypothesized that DNA methylation patterns may contribute to the development of active pulmonary tuberculosis (TB). Illumina’s DNA methylation 450 K assay was used to identify differentially methylated loci (DML) in a discovery cohort of 12 active pulmonary TB patients and 6 healthy subjects (HS)...
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ftdoajarticles:oai:doaj.org/article:24ade0aaa9644b25bd683499990ca814 2023-05-15T16:02:06+02:00 Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes Yung-Che Chen Chang-Chun Hsiao Ting-Wen Chen Chao-Chien Wu Tung-Ying Chao Sum-Yee Leung Hock-Liew Eng Chiu-Ping Lee Ting-Ya Wang Meng-Chih Lin 2020-04-01T00:00:00Z https://doi.org/10.3390/ijms21093180 https://doaj.org/article/24ade0aaa9644b25bd683499990ca814 EN eng MDPI AG https://www.mdpi.com/1422-0067/21/9/3180 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067 doi:10.3390/ijms21093180 1422-0067 1661-6596 https://doaj.org/article/24ade0aaa9644b25bd683499990ca814 International Journal of Molecular Sciences, Vol 21, Iss 3180, p 3180 (2020) pulmonary TB whole genome DNA methylation PARP9 miR505 RASGRP4 GNG12 Biology (General) QH301-705.5 Chemistry QD1-999 article 2020 ftdoajarticles https://doi.org/10.3390/ijms21093180 2022-12-31T01:18:46Z We hypothesized that DNA methylation patterns may contribute to the development of active pulmonary tuberculosis (TB). Illumina’s DNA methylation 450 K assay was used to identify differentially methylated loci (DML) in a discovery cohort of 12 active pulmonary TB patients and 6 healthy subjects (HS). DNA methylation levels were validated in an independent cohort of 64 TB patients and 24 HS. Microarray analysis identified 1028 DMLs in TB patients versus HS, and 3747 DMLs in TB patients after versus before anti-TB treatment, while autophagy was the most enriched signaling pathway. In the validation cohort, PARP9 and miR505 genes were hypomethylated in the TB patients versus HS, while RASGRP4 and GNG12 genes were hypermethylated, with the former two further hypomethylated in those with delayed sputum conversion, systemic symptoms, or far advanced lesions. MRPS18B and RPTOR genes were hypomethylated in TB patients with pleural involvement. RASGRP4 gene hypermethylation and RPTOR gene down-regulation were associated with high mycobacterial burden. TB patients with WIPI2 / GNG12 hypermethylation or MRPS18B / FOXO3 hypomethylation had lower one-year survival. In vitro ESAT6 and CFP10 stimuli of THP-1 cells resulted in DNA de-methylation changes of the PARP9 , RASGRP4 , WIPI2 , and FOXO3 genes. In conclusions, aberrant DNA methylation over the PARP9/miR505/RASGRP4/GNG12 genes may contribute to the development of active pulmonary TB disease and its clinical phenotypes, while aberrant DNA methylation over the WIPI2 / GNG12 / MARPS18B / FOXO3 genes may constitute a determinant of long-term outcomes. Article in Journal/Newspaper DML Directory of Open Access Journals: DOAJ Articles International Journal of Molecular Sciences 21 9 3180 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
pulmonary TB whole genome DNA methylation PARP9 miR505 RASGRP4 GNG12 Biology (General) QH301-705.5 Chemistry QD1-999 |
spellingShingle |
pulmonary TB whole genome DNA methylation PARP9 miR505 RASGRP4 GNG12 Biology (General) QH301-705.5 Chemistry QD1-999 Yung-Che Chen Chang-Chun Hsiao Ting-Wen Chen Chao-Chien Wu Tung-Ying Chao Sum-Yee Leung Hock-Liew Eng Chiu-Ping Lee Ting-Ya Wang Meng-Chih Lin Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes |
topic_facet |
pulmonary TB whole genome DNA methylation PARP9 miR505 RASGRP4 GNG12 Biology (General) QH301-705.5 Chemistry QD1-999 |
description |
We hypothesized that DNA methylation patterns may contribute to the development of active pulmonary tuberculosis (TB). Illumina’s DNA methylation 450 K assay was used to identify differentially methylated loci (DML) in a discovery cohort of 12 active pulmonary TB patients and 6 healthy subjects (HS). DNA methylation levels were validated in an independent cohort of 64 TB patients and 24 HS. Microarray analysis identified 1028 DMLs in TB patients versus HS, and 3747 DMLs in TB patients after versus before anti-TB treatment, while autophagy was the most enriched signaling pathway. In the validation cohort, PARP9 and miR505 genes were hypomethylated in the TB patients versus HS, while RASGRP4 and GNG12 genes were hypermethylated, with the former two further hypomethylated in those with delayed sputum conversion, systemic symptoms, or far advanced lesions. MRPS18B and RPTOR genes were hypomethylated in TB patients with pleural involvement. RASGRP4 gene hypermethylation and RPTOR gene down-regulation were associated with high mycobacterial burden. TB patients with WIPI2 / GNG12 hypermethylation or MRPS18B / FOXO3 hypomethylation had lower one-year survival. In vitro ESAT6 and CFP10 stimuli of THP-1 cells resulted in DNA de-methylation changes of the PARP9 , RASGRP4 , WIPI2 , and FOXO3 genes. In conclusions, aberrant DNA methylation over the PARP9/miR505/RASGRP4/GNG12 genes may contribute to the development of active pulmonary TB disease and its clinical phenotypes, while aberrant DNA methylation over the WIPI2 / GNG12 / MARPS18B / FOXO3 genes may constitute a determinant of long-term outcomes. |
format |
Article in Journal/Newspaper |
author |
Yung-Che Chen Chang-Chun Hsiao Ting-Wen Chen Chao-Chien Wu Tung-Ying Chao Sum-Yee Leung Hock-Liew Eng Chiu-Ping Lee Ting-Ya Wang Meng-Chih Lin |
author_facet |
Yung-Che Chen Chang-Chun Hsiao Ting-Wen Chen Chao-Chien Wu Tung-Ying Chao Sum-Yee Leung Hock-Liew Eng Chiu-Ping Lee Ting-Ya Wang Meng-Chih Lin |
author_sort |
Yung-Che Chen |
title |
Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes |
title_short |
Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes |
title_full |
Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes |
title_fullStr |
Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes |
title_full_unstemmed |
Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9 / miR-505 / RASGRP4 / GNG12 Gene Methylation and Clinical Phenotypes |
title_sort |
whole genome dna methylation analysis of active pulmonary tuberculosis disease identifies novel epigenotypes: parp9 / mir-505 / rasgrp4 / gng12 gene methylation and clinical phenotypes |
publisher |
MDPI AG |
publishDate |
2020 |
url |
https://doi.org/10.3390/ijms21093180 https://doaj.org/article/24ade0aaa9644b25bd683499990ca814 |
genre |
DML |
genre_facet |
DML |
op_source |
International Journal of Molecular Sciences, Vol 21, Iss 3180, p 3180 (2020) |
op_relation |
https://www.mdpi.com/1422-0067/21/9/3180 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067 doi:10.3390/ijms21093180 1422-0067 1661-6596 https://doaj.org/article/24ade0aaa9644b25bd683499990ca814 |
op_doi |
https://doi.org/10.3390/ijms21093180 |
container_title |
International Journal of Molecular Sciences |
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21 |
container_issue |
9 |
container_start_page |
3180 |
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1766397712563961856 |