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

Authors: Wong, Jason Y Y; De Vivo, Immaculata; Lin, Xihong; Grashow, Rachel; Cavallari, Jennifer; Christiani, David C

Published In Genet Epidemiol, (2014 Apr)

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.

PubMed ID: 24616077 Exiting the NIEHS site

MeSH Terms: Adult; Alu Elements/genetics; DNA Methylation*/drug effects; Epigenesis, Genetic/drug effects; Humans; Leukocytes/drug effects; Leukocytes/metabolism; Long Interspersed Nucleotide Elements/genetics; Longitudinal Studies; Male; Massachusetts; Metals, Heavy/adverse effects; Metals, Heavy/analysis; Metals, Heavy/chemistry; Metals, Heavy/pharmacology; Models, Genetic; Nails/chemistry; Occupations*; Particulate Matter/adverse effects; Particulate Matter/chemistry; Particulate Matter/pharmacology; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA; Telomere/drug effects; Telomere/genetics*; Telomere/metabolism*; Time Factors

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