Nicotine metabolism and clearance are endophenotypes associated with nicotine dependence [37, 38], and cigarette consumption [6, 16, 18]. The ability to genetically assess nicotine metabolism will allow for a more precise determination of the role of metabolism in smoking behaviors. We propose a predictive model of nicotine metabolism based on CYP2A6 genotype. The majority of variation in nicotine metabolism in the sample described was accounted for by seven polymorphisms. In addition, gender was associated with a modest induction of metabolism. Current smoking was also associated, albeit more weakly, with a modest induction of nicotine metabolism. Other unique outcomes of this study include the characterization of the CYP2A6/CYP2A7 gene conversion, CYP2A6*12, as a likely null allele statistically indistinguishable from CYP2A6*4 and *2(rs1801272 L160H), and the demonstration that the *1B 3′ UTR conversion has a negligible effect on in vivo CYP2A6 activity, once the polymorphism at position 51 (rs1137115) is taken into account.
