The rate of alcohol metabolism can also be affected by regulatory variations that influence the amount of enzyme present. Several studies have reported regulatory variations of the ADHs. 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 [21]. This variation has been associated with the risk for alcoholism in a Brazilian population [22]. Polymorphisms that affect expression levels were also identified in a regulatory element 3 kb upstream of ADH1C promoter [23]. Non-coding variations in and near other ADH genes have been associated with alcohol consumption and the risk for alcoholism [1, 24–27].
