Abstract
Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects. (2) Functional enrichment analysis and construction of differential methylation gene regulatory networks were performed. (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray dataset. (4) Correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNAs matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes—s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interesting different expression positions [differentially methylated positions (DMPs)] and their corresponding gene expression, we found that methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expressions in obese subjects were validated in a separate microarray dataset.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.
Highlights
With continuous improvement of living conditions, many countries have to pay more attention to the prevalence of obesity because obesity has reached the proportion of epidemic that is still rising [1]
Obesity is implicated in Methylated Genes and Obesity many diseases, such as metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), hypertension, arteriosclerosis, cardiovascular disease (CVD), and so on [3], and incurs heavy economic burdens on countries around the world [4]
Our study revealed that elevated levels of S100 calcium-binding protein A8 (S100A8)/S100 calcium-binding protein A9 (S100A9) were closely associated with the development of obesity, while hypomethylation of the promoter region resulted in upregulation of S100A8/S100A9 expression
Summary
With continuous improvement of living conditions, many countries have to pay more attention to the prevalence of obesity because obesity has reached the proportion of epidemic that is still rising [1]. Obesity is implicated in Methylated Genes and Obesity many diseases, such as metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), hypertension, arteriosclerosis, cardiovascular disease (CVD), and so on [3], and incurs heavy economic burdens on countries around the world [4]. With the deepening of research, epigenetics has emerged as a bridge between genes and environmental factors. It can change gene expression and induce longterm changes in phenotype and disease susceptibility [6]. Changes in gene methylation changes can alter the transcription of genes resulting in abnormal gene expression and eventually obesity [8]. To explore the association of DNA methylation and gene expression in the pathology of obesity
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