Cargando…
The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes
Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510364/ https://www.ncbi.nlm.nih.gov/pubmed/26196382 http://dx.doi.org/10.1371/journal.pone.0133909 |
_version_ | 1782382152077279232 |
---|---|
author | Cho, Yoon Hee Woo, Hae Dong Jang, Yoonhee Porter, Virginia Christensen, Sonja Hamilton, Raymond F. Chung, Hai Won |
author_facet | Cho, Yoon Hee Woo, Hae Dong Jang, Yoonhee Porter, Virginia Christensen, Sonja Hamilton, Raymond F. Chung, Hai Won |
author_sort | Cho, Yoon Hee |
collection | PubMed |
description | Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drinking status and the presence of centromere positive micronuclei (MNC+)—a biomarker for age-dependent genomic instability. Genomic hypomethylation of the repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers using the pyrosequencing assay. We also measured MNC+ with the micronucleus-centromere assay using a pan-centromeric probe. Possibly due to the small sample size and resulting low statistical power, smoking and drinking status had no significant effect on LINE-1 hypomethylation or the occurrence of MNC+. Consequently, we did not include them in further analyses. In contrast, LINE-1 hypomethylation and age significantly predicted MNC+; therefore, we examined whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since genomic hypomethylation is associated with genomic instability. However, LINE-1 hypomethylation did not significantly mediate the effect of age on MNC+. Our data indicate that the repetitive element LINE-1 is demethylated with age and increasing MNC+ frequency, but additional studies are needed to fully understand the relation between genomic DNA hypomethylation, age and genomic instability. |
format | Online Article Text |
id | pubmed-4510364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45103642015-07-24 The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes Cho, Yoon Hee Woo, Hae Dong Jang, Yoonhee Porter, Virginia Christensen, Sonja Hamilton, Raymond F. Chung, Hai Won PLoS One Research Article Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drinking status and the presence of centromere positive micronuclei (MNC+)—a biomarker for age-dependent genomic instability. Genomic hypomethylation of the repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers using the pyrosequencing assay. We also measured MNC+ with the micronucleus-centromere assay using a pan-centromeric probe. Possibly due to the small sample size and resulting low statistical power, smoking and drinking status had no significant effect on LINE-1 hypomethylation or the occurrence of MNC+. Consequently, we did not include them in further analyses. In contrast, LINE-1 hypomethylation and age significantly predicted MNC+; therefore, we examined whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since genomic hypomethylation is associated with genomic instability. However, LINE-1 hypomethylation did not significantly mediate the effect of age on MNC+. Our data indicate that the repetitive element LINE-1 is demethylated with age and increasing MNC+ frequency, but additional studies are needed to fully understand the relation between genomic DNA hypomethylation, age and genomic instability. Public Library of Science 2015-07-21 /pmc/articles/PMC4510364/ /pubmed/26196382 http://dx.doi.org/10.1371/journal.pone.0133909 Text en © 2015 Cho et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Cho, Yoon Hee Woo, Hae Dong Jang, Yoonhee Porter, Virginia Christensen, Sonja Hamilton, Raymond F. Chung, Hai Won The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes |
title | The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes |
title_full | The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes |
title_fullStr | The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes |
title_full_unstemmed | The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes |
title_short | The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes |
title_sort | association of line-1 hypomethylation with age and centromere positive micronuclei in human lymphocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510364/ https://www.ncbi.nlm.nih.gov/pubmed/26196382 http://dx.doi.org/10.1371/journal.pone.0133909 |
work_keys_str_mv | AT choyoonhee theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT woohaedong theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT jangyoonhee theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT portervirginia theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT christensensonja theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT hamiltonraymondf theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT chunghaiwon theassociationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT choyoonhee associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT woohaedong associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT jangyoonhee associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT portervirginia associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT christensensonja associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT hamiltonraymondf associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes AT chunghaiwon associationofline1hypomethylationwithageandcentromerepositivemicronucleiinhumanlymphocytes |