PTPRS and PER3 methylation levels are associated with childhood obesity: results from a genome-wide methylation analysis.

Abstract

The global prevalence of childhood overweight and obesity has increased in the last years. Epigenetic dysregulation affecting gene expression could be a determinant in early-life obesity onset and accompanying complications. The aim of the present investigation was to analyse the putative association between DNA methylation and childhood obesity. DNA was isolated from white blood cells of 24 children obtained from the GENOI study and was hybridized in a 450K methylation array. Two CpG sites associated with obesity were validated in 91 children by MassArray® EpiTyper™ technology. Genome-wide analysis identified 734 CpGs (783 genes) differentially methylated between cases (n=12) and controls (n=12). Ingenuity Pathway Analysis showed that these genes were involved in oxidative stress and circadian rhythm signalling pathways. Moreover, the DNA methylation levels of VIPR2, GRIN2D, ADCYAP1R1, PER3 and PTPRS regions correlated with the obesity trait. EpiTyper™ validation also identified significant correlations between methylation levels of CpG sites on PTPRS and PER3 with BMI z-score. This study identified several CpG sites and specifically several CpGs in the PTPRS and PER3 genes differentially methylated between obese and non-obese children, suggesting a role for DNA methylation concerning development of childhood obesity.