The early environment, acting via epigenetic processes, is associated with differential risk of cardio-metabolic disease (CMD) which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analysed DNA methylation in the peroxisomal proliferator-γ-co-activator-1α promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years by pyrosequencing. Body composition was measured annually by dual x-ray absorptiometry, physical activity by accelerometery and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven CpG loci were identified that showed no significant temporal change or association with leukocyte populations. Modelling using generalised estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing and activity. Methylation of one predictive locus modified binding of the pro-adipogenic PBX-1/HOXB9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.
- Received May 3, 2013.
- Accepted March 6, 2014.
- © 2014 by the American Diabetes Association.
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