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Global methylation, oxidative stress, and relative telomere length in biliary atresia patients
Alu and LINE-1 elements are retrotransposons with a ubiquitous presence in the human genome that can cause genomic instability, specifically relating to telomere length. Genotoxic agents may induce methylation of retrotransposons, in addition to oxidative DNA damage in the form of 8-hydroxy-2′-deoxy...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886632/ https://www.ncbi.nlm.nih.gov/pubmed/27243754 http://dx.doi.org/10.1038/srep26969 |
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author | Udomsinprasert, Wanvisa Kitkumthorn, Nakarin Mutirangura, Apiwat Chongsrisawat, Voranush Poovorawan, Yong Honsawek, Sittisak |
author_facet | Udomsinprasert, Wanvisa Kitkumthorn, Nakarin Mutirangura, Apiwat Chongsrisawat, Voranush Poovorawan, Yong Honsawek, Sittisak |
author_sort | Udomsinprasert, Wanvisa |
collection | PubMed |
description | Alu and LINE-1 elements are retrotransposons with a ubiquitous presence in the human genome that can cause genomic instability, specifically relating to telomere length. Genotoxic agents may induce methylation of retrotransposons, in addition to oxidative DNA damage in the form of 8-hydroxy-2′-deoxyguanosine (8-OHdG). Methylation of retrotransposons induced by these agents may contribute to biliary atresia (BA) etiology. Here, we investigated correlations between global methylation, 8-OHdG, and relative telomere length, as well as reporting on Alu and LINE-1 hypomethylation in BA patients. Alu and LINE-1 hypomethylation were found to be associated with elevated risk of BA (OR = 4.07; 95% CI: 2.27–7.32; P < 0.0001 and OR = 3.51; 95% CI: 1.87–6.59; P < 0.0001, respectively). Furthermore, LINE-1 methylation was associated with liver stiffness in BA patients (β coefficient = −0.17; 95% CI: −0.24 to −0.10; P < 0.0001). Stratified analysis revealed negative correlations between Alu and LINE-1 methylation and 8-OHdG in BA patients (P < 0.0001). In contrast, positive relationships were identified between Alu and LINE-1 methylation and relative telomere length in BA patients (P < 0.0001). These findings suggest that retrotransposon hypomethylation is associated with plasma 8-OHdG and telomere length in BA patients. |
format | Online Article Text |
id | pubmed-4886632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48866322016-06-08 Global methylation, oxidative stress, and relative telomere length in biliary atresia patients Udomsinprasert, Wanvisa Kitkumthorn, Nakarin Mutirangura, Apiwat Chongsrisawat, Voranush Poovorawan, Yong Honsawek, Sittisak Sci Rep Article Alu and LINE-1 elements are retrotransposons with a ubiquitous presence in the human genome that can cause genomic instability, specifically relating to telomere length. Genotoxic agents may induce methylation of retrotransposons, in addition to oxidative DNA damage in the form of 8-hydroxy-2′-deoxyguanosine (8-OHdG). Methylation of retrotransposons induced by these agents may contribute to biliary atresia (BA) etiology. Here, we investigated correlations between global methylation, 8-OHdG, and relative telomere length, as well as reporting on Alu and LINE-1 hypomethylation in BA patients. Alu and LINE-1 hypomethylation were found to be associated with elevated risk of BA (OR = 4.07; 95% CI: 2.27–7.32; P < 0.0001 and OR = 3.51; 95% CI: 1.87–6.59; P < 0.0001, respectively). Furthermore, LINE-1 methylation was associated with liver stiffness in BA patients (β coefficient = −0.17; 95% CI: −0.24 to −0.10; P < 0.0001). Stratified analysis revealed negative correlations between Alu and LINE-1 methylation and 8-OHdG in BA patients (P < 0.0001). In contrast, positive relationships were identified between Alu and LINE-1 methylation and relative telomere length in BA patients (P < 0.0001). These findings suggest that retrotransposon hypomethylation is associated with plasma 8-OHdG and telomere length in BA patients. Nature Publishing Group 2016-05-31 /pmc/articles/PMC4886632/ /pubmed/27243754 http://dx.doi.org/10.1038/srep26969 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Udomsinprasert, Wanvisa Kitkumthorn, Nakarin Mutirangura, Apiwat Chongsrisawat, Voranush Poovorawan, Yong Honsawek, Sittisak Global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
title | Global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
title_full | Global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
title_fullStr | Global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
title_full_unstemmed | Global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
title_short | Global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
title_sort | global methylation, oxidative stress, and relative telomere length in biliary atresia patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886632/ https://www.ncbi.nlm.nih.gov/pubmed/27243754 http://dx.doi.org/10.1038/srep26969 |
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