of CHRNA6. In this study, the association with alcohol is with SNPs in intron 2 of CHRNA6 and intron 1 of CHRNB3, with only a moderate level of association with exon 6 of CHRNA6 and no association with the upstream areas of CHRNB3. Nicotine acts at the binding site of nAChRs whereas ethanol is believed to act allosterically to modulate receptor sensitivity. Therefore, the finding that SNPs in different regions of the subunit genes are associated with different drug behaviors is consistent with idea that distinct molecular mechanisms may be associated uniquely with the two different substances. This would suggest that these polymorphisms have a direct effect on alcohol behavior beyond a correlation with tobacco use, although additional human genetic research followed by functional studies will be necessary to tease this apart.
