QTL Alc18 contained 6 significant genes (Ezh2, Gstk1, Gng12, Arhgap25, Tmem176a, and Tmem176b) altered by excessive binge drinking (Table 2), 2 of which (Tmem176a, Tmem176b) were also common in the differences between the alcohol-naïve P vs. NP rats (Table 5). Tmem176a and Tmem176b are trans-membrane proteins involved in the immune system (Cuajungco et al., 2012). Ezh2 is the catalytic subunit of Polycomb repressive complex, which is a highly conserved histone methyltransferase that targets lysine-27 of histone H3 (Simon and Lange, 2008). Gstk1 (glutathione S-transferase kappa 1), located in mitochondria and peroxisomes, is involved in energy and lipid metabolism (Morel and Aninat, 2011). Gng12 (guanine nucleotide binding protein, gamma 12) is a negative regulator of the inflammatory response (Larson et al., 2010). Arhgap25 (Rho GTPase activating protein 25) is a member of the RhoGAP family, which are negative regulators of Rho family GTPases implicated in actin remodeling (Katoh and Katoh, 2004). Further research is required to determine how these genes could impact a predisposition for high alcohol drinking or be involved in maintaining high alcohol consumption.
