the risk for alcohol dependence between 5 and 8-fold (Edenberg, 2007). Variations in cis-regulatory elements that affect the levels of ADH enzymes have also been associated with alcoholism. A SNP at position −136 (relative to the +1 translational start site) in the promoter of the ADH4 gene affects the promoter activity in hepatoma cells, with the A allele having 2-fold higher activity than the C allele (Edenberg et al., 1999). This SNP has been associated with alcohol dependence in a Brazilian population (Guindalini et al., 2005). In the Japanese population (with ALDH2*487Glu/Glu genotype) lower blood alcohol levels were observed in people with this variation (Kimura et al., 2009).
