Genetics contribute to risk of addiction with alcoholism being the most studied and experimentally established addiction with a significant genetic risk. Genes explain about 50% of the risk of alcohol addiction (Schuckit 2009). Interestingly, polymorphisms of Cyp2E1, an enzyme that metabolizes ethanol is associated with risk for alcoholism (Webb et al. 2010). In vivo, Cyp2E1 is highly expressed in monocyte-like cells where ethanol is immediately sensed through osmotic and Cyp2E1 metabolism. Cyp2E1 metabolism of ethanol increases ROS that activate proinflammatory NF-κB responses (Cao et al. 2005) (Fig. 2). Other human studies have found a direct link of NF-κB p50 to alcohol dependence (Flatscher-Bader et al. 2005; Okvist et al. 2007;Taylor et al. 2008). Polymorphisms in the precursor gene (NF-κB 1) of the NF-κB p50 subunit associate with risk for alcoholism (Taylor et al. 2008). Alleles of TNFα that increase expression have been linked to alcoholism and alcoholic liver disease (Pastor et al. 2000; Powell et al. 2000; Pastor et al. 2005). Alleles of IL-10 have also been linked to alcoholism (Pastor et al. 2000). Interestingly, in both cases alleles associated
