TY - JOUR
T1 - The association of LINE-1 hypomethylation with age and centromere positive micronuclei in human lymphocytes
AU - Cho, Yoon Hee
AU - Woo, Hae Dong
AU - Jang, Yoonhee
AU - Porter, Virginia
AU - Christensen, Sonja
AU - Hamilton, Raymond F.
AU - Chung, Hai Won
N1 - Publisher Copyright:
© 2015 Cho et al. 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.
PY - 2015/7/21
Y1 - 2015/7/21
N2 - 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 inWBC 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.
AB - 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 inWBC 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.
UR - http://www.scopus.com/inward/record.url?scp=84941287148&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0133909
DO - 10.1371/journal.pone.0133909
M3 - Article
C2 - 26196382
AN - SCOPUS:84941287148
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e0133909
ER -
