Genome-wide methylation analysis identifies ELOVL5 as an epigenetic biomarker for the risk of type 2 diabetes mellitus
Year: 2018
Type: article
Study design: Observational Study
Abstract: Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites. In a follow-up replication study (17 MZTW pairs) for external validation, we replicated the T2D-association at a novel CpG signal in the ELOVL fatty acid elongase 5 (ELOVL5) gene specific to T2D-discordant MZTW. For concordant DNA methylation signatures in tissues, we further confirmed that a CpG site (cg18681426) was associated with adipogenic differentiation between human preadipocytes and adipocytes isolated from the same biopsy sample. In addition, the ELOVL5 gene was significantly differentially expressed in adipose tissues from unrelated T2D patients and in human pancreatic islets. Our results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. Moreover, ELOVL5 expression was increased in cellular and mouse models of induced obesity-related diabetes. These findings may provide new insights into epigenetic architecture by uncovering methylation-based biomarkers.
Source: Scientific Reports
Institutions: Korea National Institute of Health, King's College London
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Wellcome Trust, National Institute for Health and Care Research, King's College London, European Commission, Centers for Disease Control and Prevention, Medical Research Council, Economic and Social Research Council, Korea National Institute of Health, Korea Centers for Disease Control and Prevention
Awards: G1515649121, G2045551132, G2335242333, NIHR Senior Investigator Award, G3016328915, G3037546023, Epigenetic Training Network - Innovative techniques and models to understand epigenetic regulation in the pathogenesis of common diseases, Epigenetic responses to social and environmental cues in early life and over the life course: impact on healthy ageing in UK population-based cohorts, G5359999036, G5863623684, G7726777033, G780947012, NIHR Senior Investigator Award, G8193312765, G8508973381
OpenAlex ID: W2894978531