Abstract
Insulin resistance (IR) is a hallmark of type 2 diabetes, metabolic syndrome and cardiometabolic risk. An epigenetic phenomena such as DNA methylation might be involved in the onset and development of systemic IR. The aim of this study was to explore the genetic DNA methylation levels in peripheral white blood cells with the objective of identifying epigenetic signatures associated with IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) following an epigenome-wide association study approach. DNA methylation levels were assessed using Infinium Methylation Assay (Illumina), and were associated with HOMA-IR values of participants from the Methyl Epigenome Network Association (MENA) project, finding statistical associations for at least 798 CpGs. A stringent statistical analysis revealed that 478 of them showed a differential methylation pattern between individuals with HOMA-IR ≤ 3 and > 3. ROC curves of top four CpGs out of 478 allowed differentiating individuals between both groups (AUC≈0.88). This study demonstrated the association between DNA methylation in some specific CpGs and HOMA-IR values that will help to the understanding and in the development of new strategies for personalized approaches to predict and prevent IR-associated diseases.
Highlights
Type 2 diabetes (T2D) is a worldwide major health concern and the most predominant type of diabetes[1]
The aim of the current work was to explore DNA methylation levels in peripheral white blood cells (PWBCs) by using an epigenome-wide association studies (EWASs) strategy with the objective of identifying epigenetic signatures associated with HOMA-Insulin resistance (IR) and identifying potential biomarkers that allow the discrimination of potentially hazardous Homeostatic Model Assessment of IR (HOMA-IR) levels
DNA methylation was significantly associated with HOMA-IR
Summary
Type 2 diabetes (T2D) is a worldwide major health concern and the most predominant type of diabetes[1]. The genetic loci identified to date only explain 5–10% of this heritability[3] In this context, available evidences suggest that epigenetics may be contributing to variations in gene expression and the risk for this metabolic disease[4]. IR is associated with a low-grade inflammation, as well as with chronic enhancement of oxidative stress, triggering endothelial dysfunction and promoting atherogenesis[4] Both genetic and epigenetic factors are involved in the development of systemic IR9. Epigenetic marks are heritable changes that cannot be explained through variations in DNA nucleotide sequence[11] These modifications are potentially reversible and can be altered by environmental factors[2], resulting in alterations of gene expression and providing an interactive connection among genetics, specific diseases and the environment[12]. Some epigenome-wide association studies (EWASs) have revealed significant associations between DNA methylation www.nature.com/scientificreports/
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