Genome-wide screen of DNA methylation identifies novel markers in childhood obesity

Abstract

Epigenetic modifications have been highlighted in chronic non-communicable diseases. The aim of this study was to investigate genome-wide DNA methylation for the identification of methylation markers in obesity. With obese Chinese preschool children, we performed comprehensive DNA methylation profiling of gene promoters and CpG islands to determine the differentially methylated genes using methylated DNA immunoprecipitation followed by hybridization to the NimbleGen Human DNA Methylation 385K Promoter Plus CpG Island Microarray. We found that compared to lean children, 251 promoters and 575 CGIs were demethylated, and 141 promoters and 277 CGIs were hypermethylated in obese children, and their distribution on chromosomes was imbalanced, showing more promoters and CGIs with demethylation on chromosomes 3, 16, 17 and 19 and more differentially methylated promoters and CGIs on chromosome X compared with chromosome Y. Further analysis indicated that aberrant methylations occurred mostly in HCP promoters and promoter CGIs. Among the top 80 promoters and CGIs that had differentiated methylation between obese and lean children, nearly half have been previously studied, and almost all of them are involved in the pathogenesis of cancers that are associated with many organs. Furthermore, four genes (FZD7, PRLHR, EXOSC4, and EIF6) with differential promoter methylation were validated, and their associations with obesity must be clarified. In conclusion, this study represents the first effort to determine methylation markers in obese Chinese children, which has potential relevance for identifying markers that are useful in elucidating the mechanisms of obesity pathogenesis and its complications.

Keywords: Children; Genome-wide DNA methylation; Obesity; Obesity-related diseases.