A),56 or presynaptic signaling and membrane trafficking (SNCA, which encodes synuclein, alpha).57 Hillemacher et al.58 compared AVP and ANP promoter DNA methylation differences between 111 AUD cases and 57 healthy controls. They reported a significant increase in AVP promoter DNA methylation but a significant decrease in ANP promoter DNA methylation in the peripheral blood of AUD subjects. A study by Bruckmann et al. with 49 AUD cases and 37 controls showed hypomethylation of GDAP1 in AUD subjects.59 Three of the above 12 genes showed hypermethylation in their promoter regions in the peripheral blood of AUD subjects: HERP (66 AUD cases/55 controls),60 OPRM1 (125 AUD cases/69 controls),61 and SNCA (84 AUD cases/93 controls).62 Four studies have examined SCL6A3 promoter DNA methylation changes in AUD subjects: two showed hypermethylation of SCL6A3 in AUD subjects or significant associations of SCL6A3 methylation and craving or alcohol cue-induced brain reactivity ([76 AUD cases/35 controls]63; [38 AUD cases/17 controls]64), while two others did not reveal significant differences in SCL6A3 promoter DNA methylation levels between cases and controls ([100 AUD cases/98 controls]65; [171 AUD cases/160 controls]66). Additionally, the association of AUDs and DNA methylation in promoter regions of five other candidate genes (GRIN2B, HCRT, SLC6A4, MAOA, and
