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The association between global DNA methylation and telomere length in a longitudinal study of boilermakers.

Authors
Wong-JYY; De-Vivo-I; Lin-X; Grashow-R; Cavallari-J; Christiani-DC
Source
Genet Epidemiol 2014 Apr; 38(3):254-264
NIOSHTIC No.
20044568
Abstract
The objectives of this study were to determine if global DNA methylation, as reflected in LINE-1 and Alu elements, is associated with telomere length and whether it modifies the rate of telomeric change. A repeated-measures longitudinal study was performed with a panel of 87 boilermaker subjects. The follow-up period was 29 months. LINE-1 and Alu methylation was determined using pyrosequencing. Leukocyte relative telomere length was assessed via real-time qPCR. Linear-mixed models were used to estimate the association between DNA methylation and telomere length. A structural equation model (SEM) was used to explore the hypothesized relationship between DNA methylation, proxies of particulate matter exposure, and telomere length at baseline. There appeared to be a positive association between both LINE-1 and Alu methylation levels, and telomere length. For every incremental increase in LINE-1 methylation, there was a statistically significant 1.0 10(-1) (95% CI: 4.6 10(-2), 1.5 10(-1), P < 0.01) unit increase in relative telomere length, controlling for age at baseline, current and past smoking status, work history, BMI (log kg/m(2) ) and leukocyte differentials. Furthermore, for every incremental increase in Alu methylation, there was a statistically significant 6.2 10(-2) (95% CI: 1.0 10(-2), 1.1 10(-1), P = 0.02) unit increase in relative telomere length. The interaction between LINE-1 methylation and follow-up time was statistically significant with an estimate -9.8 10(-3) (95% CI: -1.8 10(-2), -1.9 10(-3), P = 0.02); suggesting that the rate of telomeric change was modified by the degree of LINE-1 methylation. No statistically significant association was found between the cumulative PM exposure construct, with global DNA methylation and telomere length at baseline.
Keywords
Humans; Men; Genetics; Drugs; Metabolism; Leukocytes; Metal-compounds; Metallic-compounds; Chemical-composition; Chemical-properties; Pharmacology; Particulates; Cancer; Cardiovascular-disease; Epidemiology; Proteins; Cell-division; Author Keywords: telomere; LINE-1; Alu; DNA methylation; longitudinal
Contact
Jason Y. Y. Wong, Departments of Epidemiology and Environmental Health, Harvard School of Public Health, Channing Division ofNetwork Medicine, 181 Longwood Avenue, Boston, MA 02115
Publication Date
20140301
Document Type
Journal Article
Funding Type
Cooperative Agreement
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U60-OH-009762; M062014
Issue of Publication
3
ISSN
0741-0395
Source Name
Genetic Epidemiology
State
MD; MA; CT
Performing Organization
CPWR - The Center for Construction Research and Training, Silver Spring, Maryland
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