Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality

Autor: Ute Mons, Ines Florath, Katja Butterbach, Ben Schöttker, Bernd Holleczek, Hermann Brenner, Christian Stock, Yan Zhang
Rok vydání: 2016
Předmět:
Zdroj: Environmental Health Perspectives
ISSN: 1552-9924
0091-6765
Popis: Background With epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified. Objectives We aimed to assess dose–response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality. Methods In a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Illumina 450K assay. Deaths were recorded during a median follow-up of 10.3 years. Dose–response relationships of smoking exposure with methylation at nine CpGs were modeled by restricted cubic spline regression. Associations of individual and aggregate methylation patterns with all-cause, cardiovascular, and cancer mortality were assessed by multiple Cox regression. Results Clear dose–response relationships with respect to current and lifetime smoking intensity were consistently observed for methylation at six of the nine CpGs. Seven of the nine CpGs were also associated with mortality outcomes to various extents. A methylation score based on the top two CpGs (cg05575921 and cg06126421) showed the strongest associations with all-cause, cardiovascular, and cancer mortality, with adjusted hazard ratios (95% CI) of 3.59 (2.10, 6.16), 7.41 (2.81, 19.54), and 2.48 (1.01, 6.08), respectively, for participants with methylation levels in the lowest quartile at both CpGs. Adding methylation at those two CpGs into a model that included the variables of the Systematic Coronary Risk Evaluation chart for fatal cardiovascular risk prediction improved the predictive discrimination. Conclusion The novel methylation biomarkers are highly informative for both smoking exposure and smoking-related mortality outcomes. In particular, these biomarkers may substantially improve cardiovascular risk prediction. Nevertheless, the findings of the present study need to be further validated in additional large longitudinal studies. Citation Zhang Y, Schöttker B, Florath I, Stock C, Butterbach K, Holleczek B, Mons U, Brenner H. 2016. Smoking-associated DNA methylation biomarkers and their predictive value for all-cause and cardiovascular mortality. Environ Health Perspect 124:67–74; http://dx.doi.org/10.1289/ehp.1409020
Databáze: OpenAIRE
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