Human candidate gene methylation studies have provided some preliminary evidence for the role of epigenetic influences in people affected with SUD. Candidate gene methylation studies of alcohol use have focused on genes whose products function in 5 major systems: (1) well-characterized neurotransmission systems (e.g., monoamine oxidase A- MAOA, serotonin transporter- SERT, dopamine transporter- DAT1, μ opioid receptor- OPRM1); (2) additional neurotransmitter systems (e.g., vasopressin and alpha natriuretic peptide- ANP); (3) one-carbon metabolism; (4) craving and symptoms of dependence (e.g., proopiomelanocortin- POMC and alpha-synuclein- SNCA); and (5) neuronal growth and homeostasis (e.g., nerve growth factor- NGF)(Andersen, Dogan, Beach, & Philibert, 2015). Generally, these studies reported weak, but significant differential methylation between affected and non-affected groups. Significant results from candidate gene association studies of smoking have reported significant results in genes whose products function in neurotransmitter metabolism, specifically MAOA and MAOB as well as catechol-O-methyltransferase – COMT). A candidate gene methylation study of the cannabinoid receptor 1 (CNR1) promoter region reported significant differences in CB1 expression when comparing cannabis dependent smokers against non-smokers as well as cigarette smokers (Rotter et al., 2012).
