Multiple variations in genes encoding alcohol dehydrogenases have been associated with the risk for alcoholism (Birley et al., 2009; Edenberg, 2007; Edenberg et al., 2006). Although the most widely-studied of these variations affect the sequence of the encoded enzymes, one (rs1800759) is known to affect regulation of gene expression (Edenberg et al., 1999). The expression level of ADH enzymes could affect the flux through the alcohol metabolic pathway, and thereby influence the effects of alcohol and the risk for alcoholism. We studied three SNPs in this region, rs7678936 (G/T), rs7678890 (T/G) and rs11401494 (del/T). They are not present in any of the transcription factor binding sites identified in this study. However, rs7678936 is adjacent to a putative FOXA site that was not tested and rs7678890 is adjacent to site 5 (HNF-1α). To explore the contribution of each SNP, we tested three haplotypes. Haplotype 2 (T, T, del) and haplotype 3 (G, G, del) had a similar fold change (0.6-fold) relative to Hap.1 (G, T, del), so we were unable to attribute the effect to a single SNP. rs11401494 had a small effect on the function of the enhancer.
