title: The association between global DNA methylation and telomere length in a longitudinal study of boilermakers.
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.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Jason Y Y
authors.initials: JY
authors.lastname: Wong
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.forename: Rachel
authors.initials: R
authors.lastname: Grashow
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cavallari
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D020087:Alu Elements / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts; D019216:Metals, Heavy / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D008957:Models, Genetic; D009262:Nails / Q000737:chemistry; D009790:Occupations; D052638:Particulate Matter / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016615:Telomere / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019216:Metals, Heavy; D052638:Particulate Matter
keywords: Alu; DNA methylation; LINE-1; longitudinal; telomere