The nicotinic receptor polymorphisms associated with response to varenicline measured from weeks 9 to 12 were not associated with continuous abstinence through the non-treatment follow-up period (including all weeks 9–52). During this period, no markers were significantly associated with continuous abstinence in the varenicline-treated smokers alone. In contrast, among the smokers treated with bupropion, CYP2B6 polymorphisms were associated with continuous abstinence from weeks 9 to 52, as well as weeks 9 to 12. In fact, this association with CYP2B6 polymorphisms extended to all smokers, regardless of treatment during the first 12 weeks. This may be due to a broader effect of CYP2B6 on nicotine dependence, independent of its role in bupropion metabolism. This interpretation is consistent with a prior study identifying an association of a functional CYP2B6 SNP with placebo response in a bupropion clinical trial (Lee et al, 2007). Alternatively, this genetic signal, although more proximate to CYP2B6, may have a more direct effect on the adjacent CYP2A6 locus, which is itself associated with continuous abstinence from weeks 9 to 52. In addition to (or perhaps because of) its
