Epigenetic effects of alcohol consumption on type 2 diabetes.

East Asians can be more susceptible to heavy alcohol consumption than others, due to genetic variations. In addition, alcohol drinking has been suspected as a cause of type 2 diabetes (T2D). To clarify the integrated toxic mechanisms of alcohol on T2D in East Asians, we performed epigenome-wide association studies using methylation profiling arrays among four groups of South Korean men (N = 80): drinking (DK), diabetic (DM), both drinking and diabetic (DK + DM), and non-drinking and non-diabetic controls (Con). We screened hypermethylated or hypomethylated sites in both DK and DM, compared to Con, and found 15 more and 10 fewer methylated sites in DK + DM than in DK or DM among the screened sites. Furthermore, we confirmed the involvement of SLC8A1, IGFBP7, ZBED3, etc., in alcohol-related diseases and T2D and observed that these epigenetic sites were related to the negative regulation of chemokines, response to hexose, transport, glucose, regulation of cell communication, response to insulin, sodium ion transmembrane transport, and sodium ion transport. MUL1, GPLD1, ZBED3, and SLC8A1 showed multiple associations with these pathways. Finally, we found that some of the 25 epigenetic sites, including CCRL2 for inflammation, ACTG1 for cell shape, and NDUFB9 for oxidoreduction, were hubs of the STRING network. In conclusion, our findings suggest that alcohol-induced T2D development involves two interconnected pathophysiological mechanisms, mitochondrial dysfunction and errors in cell communication and ion transport that contribute to pancreatic β-cell failure.