Ethanol induced hyperhomocysteinemia and its NMDA-agonistic byproducts have been suggested as a possible predictor of ethanol withdrawal seizures (Bleich et al., 2004). Elevated homocysteine levels in the blood of alcoholic patients have been associated with hypermethylation at the promoter of the homocysteine-induced endoplasmic reticulum protein gene, corresponding to lower mRNA expression in the blood cells (Bleich et al., 2006). Elevated homocysteine levels have also been implicated in hypermethylation of the alpha-synuclein gene promoter, which may be responsible for altered mRNA and protein expression and was linked to alcohol craving (Bönsch et al., 2004; 2005; Bönsch, Greifenberg, et al., 2005). Chronic alcohol consumption could be associated with altered methylation patterns of various genes acting via s-adenosylmethionine (SAM) metabolism and altering homocysteine levels. Approaches that can detect altered transcripts and corresponding changes in methylation levels peripheral blood samples such as lymphocytes and mononuclear cells can be used as potential tool for the development of biomarkers (Biermann et al., 2009; Hillemacher et al., 2009; Zhang et al., 2013; Zhao et al., 2013).
