DNA hydroxymethylation-mediated epigenetic modifications in alcohol use disorder

Alcohol use disorder (AUD) is a chronic neuropsychiatric condition that causes an increased risk of dementia and deaths worldwide. Evidence indicates that alcohol misuse can induce changes in genetic factors. Alcohol-induced DNA epigenetic modification alters brain function and contributes to AUD. Among these modifications, DNA methylation is highly implicated in AUD; however, 5-hydroxymethylation of 5-methylcytosine mediated by ten-eleven translocation (TET) enzymes produces 5-hydroxymethylcytosine (5hmC), which has emerged as a stable epigenetic mark. Recent studies have shown that 5hmC at gene promoters can influence gene expression, especially of genes related to neurotransmitter signaling, alcohol addiction, and cognition. In this review, we summarize findings of TETs-mediated 5-hydroxymethylation in AUD, with special emphasis on the brain and liver. Furthermore, we highlight the key challenges and research gaps in understanding the underlying mechanisms of TETs/5hmC-mediated epigenetic modification in AUD.