Type 1 diabete
s (T1D)
show
s 鈭?0% concordance rate in monozygotic twin
s (MZ)
sugge
sting a role for environmental factor
s and/or epigenetic modification
s in the etiology of the di
sea
se. The aim of our
study wa
s to di
ssect the contribution of epigenetic factor
s, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell line
s from 3 monozygotic (MZ) twin pair
s di
scordant for T1D and 6 MZ twin pair
s concordant for the di
sea
se u
sing HumanMethylation27 BeadChip. Thi
s a
ssay a
sse
sse
s the methylation
state of 27,578 CpG
site
s, mo
stly located within proximal promoter region
s. We identified 88 CpG
site
s di
splaying
significant methylation change
s in all T1D-di
scordant MZ twin pair
s. Functional annotation of the gene
s with di
stinct CpG methylation profile
s in T1D
sample
s showed differential DNAm of immune re
spon
se and defen
se re
spon
se pathway
s between affected and unaffected twin
s. Integration of DNAm data with GWAS data mapped
several known T1D a
ssociated gene
s, HLA, INS, IL-2RB, CD226, which
showed
significant difference
s in DNAm between affected and unaffected of twin
s.
Our findings suggest that abnormalities of DNA methylation patterns, known to regulate gene transcription, may be involved in the pathogenesis of T1D.