The ADH4 gene encodes π-alcohol dehydrogenase, which has a Km for ethanol of 34 mM (Li et al., 1977). In addition to ethanol, it can also carry out the oxidation and reduction of long-chain aliphatic alcohols and aromatic aldehydes (Edenberg and Bosron, 1997). The transcript is expressed at highest levels in liver, both fetal and adult, and at much lower levels in gastrointestinal tract, stomach and spleen (Edenberg, 2000). The proximal promoter of ADH4 has multiple transcription factor binding sites including members of the C/EBP family and AP-1 family (Li and Edenberg, 1998).The known cis-regulatory elements upstream of ADH4 do not completely account for its expression levels in the liver. Because polymorphisms in regulatory sequences may play a critical role in affecting the genetic risks for alcoholism, understanding the regulation of ADH expression is important. In this study, we have identified and characterized a distal regulatory element upstream of the ADH4 gene. We also studied the effects of polymorphisms on the function of this regulatory region.
