TABLE 2.

Promoter DNA Methylation Levels of Diabetes Mellitus-Related Genes Associated with Urinary Arsenical Concentrations

Gene symbol	Gene name	Promoter methylation change with increasing urinary arsenical (ng/ml)	Arsenical group (ng/ml)	Association with diabetes mellitus (DM)
GAD1	glutamate decarboxylase 1	hypomethylation	MMAs	Major β cell autoantigen in T1DM [43]
INPPL1	inositol polyphosphate phosphatase-like 1	hypomethylation	iAs MMAs	Negative regulator of insulin signaling [46]; expression associated with insulin resistance [70]
INS	insulin	hypomethylation	MMAs	Promotes glucose uptake from blood into peripheral tissues [71]
IRF1	interferon regulatory factor 1	hypomethylation	MMAs	Promotes β cell apoptosis [41]
MAP3K1	mitogen-activated protein kinase kinase kinase 1	hypomethylation	DMAs	Promotes β cell apoptosis [52]
PDX1	pancreatic and duodenal homeobox 1	hypomethylation	DMAs	Transcriptional activator of insulin gene; important in β cell differentiation, development, function and survival [50, 51]
PRKCD	protein kinase C delta	hypermethylation	DMAs	Promotes β cell apoptosis [53]; regulates insulin signaling [54]
TNFRSF1B	tumor necrosis factor receptor superfamily, member 1B	hypomethylation	MMAs	Regulator of TNFa-mediated apoptosis [72]; levels of plasma soluble fraction of receptor positively correlated with insulin resistance [45], severity of diabetic retinopathy [73], and predicting risk of end stage renal disease [74], and chronic kidney disease [75] in diabetics
TRAF6	TNF receptor-associated factor 6	hypomethylation	MMAs	Promotes β-cell apoptosis [42]
SOCS6	suppressor of cytokine signaling 6	hypomethylation	MMAs	Regulator of insulin signaling [47, 48]
VAMP2	vesicle-associated membrane protein 2	hypomethylation	MMAs	Minor antigen in T1DM [44]; involved in translocation of glucose transporter to cell membrane, overexpressed in insulin-resistant tissue [49]