Genome-wide Methylation Analysis Identifies ELOVL5 As an Epigenetic Biomarker for the Risk of Type 2 Diabetes Mellitus

Overview

Journal Sci Rep

Specialty Science

Date 2018 Oct 7

PMID 30291282

Citations 9

Authors

Joo-Yeon Hwang

Hyo Jung Lee

Min Jin Go

Han Byul Jang

Nak-Hyun Choi

Jae Bum Bae

Juan E Castillo-Fernandez

Jordana T Bell

Tim D Spector

Hye-Ja Lee

Bong-Jo Kim

Affiliations

Soon will be listed here.

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.

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