CYP2A6*12 is a hybrid allele that consists of the 5′ flanking region and first two exons of CYP2A7, and the remaining seven exons and 3′ flanking region of CYP2A6. CYP2A7 mRNA is reported to be highly expressed, although the resulting protein has no identified enymatic activity [43]. CYP2A6*12 allele carriers were previously reported to display reduced in vivo coumarin 7-hydroxylation, and this was confirmed by cell culture experiments [19]. Although earlier publications have chosen to categorize *12 with intermediate function alleles, i.e. *9 [15, 44] regarding nicotine metabolism, they did not demonstrate a significant difference between *12 and the null alleles, *2 and *4. Our evidence suggests that *12 is more similar to *2 and *4 than to *9. These distinctions held true for all metabolism metrics tested at all time points, including the log ratios of deuterated and ad libitum 3′-trans-hydroxycotinine/cotinine. That is, parameter estimates for *12 were statistically significantly different from normal function alleles, but not from *2 and *4, whereas estimates for the *9 and *1A(51A) alleles were significantly different from both normal and *2/*4 alleles (data
