DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology

Mihaela Stefan, Weijia Zhang, Erlinda Concepcion, Zhengzi Yi, Yaron Tomer

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Type 1 diabetes (T1D) shows ~40% concordance rate in monozygotic twins (MZ) suggesting a role for environmental factors and/or epigenetic modifications in the etiology of the disease. The aim of our study was to dissect the contribution of epigenetic factors, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell lines from 3 monozygotic (MZ) twin pairs discordant for T1D and 6 MZ twin pairs concordant for the disease using HumanMethylation27 BeadChip. This assay assesses the methylation state of 27,578 CpG sites, mostly located within proximal promoter regions. We identified 88 CpG sites displaying significant methylation changes in all T1D-discordant MZ twin pairs. Functional annotation of the genes with distinct CpG methylation profiles in T1D samples showed differential DNAm of immune response and defense response pathways between affected and unaffected twins. Integration of DNAm data with GWAS data mapped several known T1D associated genes, HLA, INS, IL-2RB, CD226, which showed significant differences in DNAm between affected and unaffected of twins. Our findings suggest that abnormalities of DNA methylation patterns, known to regulate gene transcription, may be involved in the pathogenesis of T1D.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalJournal of Autoimmunity
Volume50
DOIs
StatePublished - May 2014
Externally publishedYes

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Keywords

  • DNA methylation
  • Monozygotic twins
  • Transcriptional regulation
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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