The Association Between Global DNA Methylation and Telomere Length in a Longitudinal Study of Boilermakers

摘要

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/m²) 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.