Table 1.

Alterations of DNA methylation in T1D

Genes	Cell types	Main findings	References
UNC13B	Whole blood	Involved in exocytosis, hypermethylation is associated with the risk of diabetic nephropathy in T1D	[96]
INS	Peripheral blood samples	DNA methylation near the INS gene is associated with INS genetic variation (rs689) and T1D	[97,98]
	Human islets	Relevant to insulin secretion
IL-2RA	WBCs or tissue samples	CpGs (-373 and -456) showed increased methylation in T1D patients, associated with Tregs	[40]
Amylin DNA	β cells in the islet	Demethylated cfDNA may serve as a biomarker of β-cell death in T1D	[86]
FOXP3	Tregs	FOXP3 promoter region was hypermethylated, FOXP3 expression was decreased, contributing to the pathogenesis of T1D	[34,41]
TNF	CD14+ cells	Hypermethylated in T1D, encodes protein TNF, a key inflammatory cytokine associated with T1D in animal models	[37]
TRAF6	CD14+ cells	Hypermethylated in T1D, involved in NF-κB and MAPK kinase activation	[37]
CD6	CD14+ cells	Hypermethylated in T1D, critical for T activation	[37]
HLA-DQB1	CD14+ cells	Hypomethylated in T1D, carries the highest single genetic risk for T1D, involved in presenting peptides from extracellular proteins	[37]
NFKBIA	CD14+ cells	Hypomethylated in T1D, an important regulator of apoptosis and inflammatory immune responses	[37]
GAD2	CD14+ cells	Hypomethylated in T1D, encodes GAD65, a major T1D autoantigen involved in disease etiology	[37]

cfDNA: Circulating free amylin DNA; T1D: Type 1 diabetes; Tregs: Regulatory T cells; WBCs: Whole blood cells.