Int. J. Environ. Res. Public Health 2010, 7 3. Genetic Predisposition 1875 Genes have been proposed to be involved in a predisposition to ALD development and alcohol use disorders. Combined genetic information about these two entities might enhance alcohol related diseases. 3.1. Candidate Genes Predisposing Alcoholic Liver Disease When ethanol is consumed, its metabolism depends almost exclusively on the liver through different enzymes capable of catalyzing the oxidation of alcohol. Polymorphisms in the two main enzymes involved in ethanol metabolism [alcohol dehydrogenase; 1B (ADH1B) and aldehyde dehydrogenase (ALDH2)] confer susceptibility to develop ALD. Alcohol is transformed into acetaldehyde through alcohol dehydrogenases, this intermediate metabolite is responsible for the toxic effects of ethanol. The next step is the metabolism of acetaldehyde to acetate (a non-toxic metabolite) through ALDH2 [9]. Either higher activity of ADH1B or lower activity of ALDH2 lead to accumulation of acetaldehyde following alcohol consumption, which, in turn, causes an unpleasant and aversive response, termed the flushing reaction, similar to the disulfiram effect [10]. Japanese, Chinese and some Jewish population constitute the main group displaying specific protective polymorphisms against the development of ALD [11]. 3.2. Candidate Genes Predisposing Alcohol Use Disorders Linkage studies have identified several chromosomal regions, supporting the involvement of loci on chromosomes in alcohol dependency, however the recognition of specific gene regions is still challenging. 3.2.1. Endophenotypes It is possible that a small number of genes might directly influence alcohol dependency. Nevertheless, it is more likely that relevant genes affect a range of endophenotypes (defined as genetically influenced intermediate characteristics). These endophenotypes will subsequently have impact in the risk for heavier drinking and alcohol-related life problems. Some of these genetically influenced characteristics are related to alcoholism, focused in treatment response [12]. In contrast to what happens with protective polymorphism in ALD, a low response to alcohol predicts increased risk of developing alcohol use disorders and has been associated with genetic variation in the serotonin transporter gene and the gene encoding γ-aminobutyric acid receptor A (GABRA) [11]. It has also been suggested that a determined gene—environmental interaction contributes to the development of AD. This occurs when exposure to an environmental factor has an effect on the health of individuals which is conditioned to their genotype. Thus, several genes have been described including monoamine oxidase A (MAOA), the serotonin transporter (HTT), catechol-O- methyltransferase (COMT), the corticotropin releasing hormones receptor 1 gene and the dopamine transporter [8,11,13–15]. The D2 dopamine receptor gene is the most widely studied and described receptor related to alcoholism [16]. One study showed that the prevalence of the DRD2 minor allele A1 (A1/A1 or A1/A2 genotype) was significantly higher in alcoholics than in nonalcoholic controls