Human genetic association studies also have directly linked certain polymorphisms of the genes encoding NF-κB to alcohol dependence (Edenberg et al. 2008; Flatscher-Bader et al. 2005; Okvist et al. 2007). For example, polymorphisms in a precursor gene called NF-kB1 that encodes one of the subunits of the transcription factor (i.e., the NF-κB p50 subunit) and which is important for activation of transcription have been associated with the risk for alcoholism (Edenberg et al. 2008). Likewise, alleles of the proinflammatory cytokine TNFα that result in increased TNFα expression have been linked to alcoholism and alcoholic liver disease (Pastor et al. 2000, 2005; Powell et al. 2000). Another genetic linkage exists between certain alleles of the anti-inflammatory, NF-κB–inhibiting cytokine IL-10 and alcoholism (Marcos et al.2008). Additional genetic evidence regarding innate immune genes and the risk for alcoholism comes from polymorphisms of the gene encoding a molecule called the IL-1 receptor antagonist as well as from multiple other alleles of the IL-1 gene complex (Saiz et al. 2009).
