Three SNPs (rs1997794, rs6045819 and rs2235749) that showed association with AD, CD or OD form a CpG dinucleotide (methylation associated SNPs). Alterations in methylation of a specific allele through epigenetic mechanisms may affect transcription. An increase in methylation levels of the C- allele of the 3′ UTR SNP rs2235749 was reported in the dorsolateral prefrontal cortex in alcohol-dependent subjects (Taqi et al. 2011). A 63 kDa protein showed differential binding affinity for the risk T-allele, and the methylated and unmethylated C-allele in the brain. The T-allele of SNP rs1997794 resides within a noncanonical AP-1-binding element and was associated with lower PDYN expression in brain cortical areas. The C-allele was shown to abrogate AP-1 binding (Yuferov et al. 2009).
