TY - JOUR
T1 - DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology
AU - Stefan, Mihaela
AU - Zhang, Weijia
AU - Concepcion, Erlinda
AU - Yi, Zhengzi
AU - Tomer, Yaron
N1 - Funding Information:
We thank the National Disease Research Interchange (NDRI, Philadelphia, PA) for providing us with the DNA samples of the diabetes twins. This work was supported in part by grants DK061659 , DK067555 & DK073681 from NIDDK (to YT). In addition this material is based upon work supported in part by the Department of Veterans Affairs , Veterans Health Administration, Office of Research and Development, and by the VA Biomedical Laboratory Research and Development Merit Award 1I01BX002031 (to YT).
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Monozygotic twins
KW - Transcriptional regulation
KW - Type 1 diabetes
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U2 - 10.1016/j.jaut.2013.10.001
DO - 10.1016/j.jaut.2013.10.001
M3 - Article
C2 - 24210274
AN - SCOPUS:84898787481
SN - 0896-8411
VL - 50
SP - 33
EP - 37
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -
