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Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa
BACKGROUND: Telomere length shortening in Helicobacter pylori (H. pylori) infected gastric mucosa constitutes the earliest steps toward neoplastic transformation. In addition to this genotoxic changes, epigenetic changes such as promoter CpG island (PCGI) methylation are frequently occurred in H. py...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190073/ https://www.ncbi.nlm.nih.gov/pubmed/27259265 http://dx.doi.org/10.18632/oncotarget.9764 |
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author | Tahara, Tomomitsu Shibata, Tomoyuki Okubo, Masaaki Kawamura, Tomohiko Horiguchi, Noriyuki Ishizuka, Takamitsu Nakano, Naoko Nagasaka, Mitsuo Nakagawa, Yoshihito Ohmiya, Naoki |
author_facet | Tahara, Tomomitsu Shibata, Tomoyuki Okubo, Masaaki Kawamura, Tomohiko Horiguchi, Noriyuki Ishizuka, Takamitsu Nakano, Naoko Nagasaka, Mitsuo Nakagawa, Yoshihito Ohmiya, Naoki |
author_sort | Tahara, Tomomitsu |
collection | PubMed |
description | BACKGROUND: Telomere length shortening in Helicobacter pylori (H. pylori) infected gastric mucosa constitutes the earliest steps toward neoplastic transformation. In addition to this genotoxic changes, epigenetic changes such as promoter CpG island (PCGI) methylation are frequently occurred in H. pylori infected gastric mucosa. The aim of this study was to investigate a potential link between H. pylori related PCGI methylation and telomere length shortening in the human gastric mucosa. METHODS: Telomere length was measured in non-neoplastic gastric mucosa from 106 cancer-free subjects. To identify H. pylori related PCGI methylation, bisulfite pyrosequencing was used to quantify the methylation of 49 PCGIs from 47 genes and LINE1 repetitive element RESULTS: We identified five PCGIs (IGF2, SLC16A12, SOX11, P2RX7 and MYOD1), which the methylation is closely associated with H. pylori infection. Hypermethylation of all these PCGIs was associated with development of pathological state from normal to mild, active, and atrophic gastritis (P<0.001) and lower pepsinogen I/II ratio (P<0.05), an indicator for gastric mucosal atrophy. Telomere shortening was significantly associated with mean Z score methylation of five PCGIs (R=−0.39, P<0.0001) and four of these locus (IGF2: R=−0.35, P=0.0003, SLC16A12: R=−0.35, P=0.0002, P2RX7: R=−0.29, P=0.003, and MYOD1: R=−0.33, P=0.0005). Multivariate analysis revealed that telomere shortening held an increased risk for hypermethylation (odds ratio: 1.71, 95% confidence interval: 1.11-2.63, P=0.016). CONCLUSION: Potential link between H. pylori related PCGI methylation and telomere shortening emphasize the importance of genotoxic-epigenetic interaction in the pathological state of H. pylori infected gastric mucosa. |
format | Online Article Text |
id | pubmed-5190073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51900732017-01-05 Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa Tahara, Tomomitsu Shibata, Tomoyuki Okubo, Masaaki Kawamura, Tomohiko Horiguchi, Noriyuki Ishizuka, Takamitsu Nakano, Naoko Nagasaka, Mitsuo Nakagawa, Yoshihito Ohmiya, Naoki Oncotarget Research Paper BACKGROUND: Telomere length shortening in Helicobacter pylori (H. pylori) infected gastric mucosa constitutes the earliest steps toward neoplastic transformation. In addition to this genotoxic changes, epigenetic changes such as promoter CpG island (PCGI) methylation are frequently occurred in H. pylori infected gastric mucosa. The aim of this study was to investigate a potential link between H. pylori related PCGI methylation and telomere length shortening in the human gastric mucosa. METHODS: Telomere length was measured in non-neoplastic gastric mucosa from 106 cancer-free subjects. To identify H. pylori related PCGI methylation, bisulfite pyrosequencing was used to quantify the methylation of 49 PCGIs from 47 genes and LINE1 repetitive element RESULTS: We identified five PCGIs (IGF2, SLC16A12, SOX11, P2RX7 and MYOD1), which the methylation is closely associated with H. pylori infection. Hypermethylation of all these PCGIs was associated with development of pathological state from normal to mild, active, and atrophic gastritis (P<0.001) and lower pepsinogen I/II ratio (P<0.05), an indicator for gastric mucosal atrophy. Telomere shortening was significantly associated with mean Z score methylation of five PCGIs (R=−0.39, P<0.0001) and four of these locus (IGF2: R=−0.35, P=0.0003, SLC16A12: R=−0.35, P=0.0002, P2RX7: R=−0.29, P=0.003, and MYOD1: R=−0.33, P=0.0005). Multivariate analysis revealed that telomere shortening held an increased risk for hypermethylation (odds ratio: 1.71, 95% confidence interval: 1.11-2.63, P=0.016). CONCLUSION: Potential link between H. pylori related PCGI methylation and telomere shortening emphasize the importance of genotoxic-epigenetic interaction in the pathological state of H. pylori infected gastric mucosa. Impact Journals LLC 2016-06-01 /pmc/articles/PMC5190073/ /pubmed/27259265 http://dx.doi.org/10.18632/oncotarget.9764 Text en Copyright: © 2016 Tahara et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Tahara, Tomomitsu Shibata, Tomoyuki Okubo, Masaaki Kawamura, Tomohiko Horiguchi, Noriyuki Ishizuka, Takamitsu Nakano, Naoko Nagasaka, Mitsuo Nakagawa, Yoshihito Ohmiya, Naoki Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa |
title | Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa |
title_full | Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa |
title_fullStr | Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa |
title_full_unstemmed | Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa |
title_short | Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa |
title_sort | demonstration of potential link between helicobacter pylori related promoter cpg island methylation and telomere shortening in human gastric mucosa |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190073/ https://www.ncbi.nlm.nih.gov/pubmed/27259265 http://dx.doi.org/10.18632/oncotarget.9764 |
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