The association between global DNA methylation and telomere length in a longitudinal study of boilermakers.
Wong-JYY; De-Vivo-I; Lin-X; Grashow-R; Cavallari-J; Christiani-DC
Genet Epidemiol 2014 Apr; 38(3):254-264
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.
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
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
CPWR - The Center for Construction Research and Training, Silver Spring, Maryland