Type B GABA receptors (GABAB), which regulate presynaptic GABA release, among other functions (Bettler et al., 2004), are also involved in the biological effects of alcohol. GABAB agonists reduce craving for alcohol (Addolorato et al., 2002), and GABAB receptor expression is down-regulated in the hippocampus of alcoholics and alcohol-preferring rats (Enoch et al., 2012). Relative to GABAA receptor subunit genes, the effects of variation in GABAB receptor genes GABBR1 and GABBR2 on alcohol use in humans have been infrequently appraised, although one study observing a non-significant trend for association with an allele in GABBR1 allowed the possibility that variation in GABAB genes may influence alcohol dependence (Sander et al., 1999). Furthermore, a number of other genes involved in GABAergic transmission but not coding for GABA receptors have also been shown to be associated with alcohol-related outcomes. For example, SNPs in one of the gene isoforms for the glutamate decarboxylase enzyme (GAD1), which is involved in GABA synthesis, have been associated with initial sensitivity to alcohol and age-of-onset of alcohol dependence (Kuo et al., 2009).
