The AGES × drug interaction was significant illustrating that smokers with different AGES scores responded differently to bupropion. As illustrated in Figure 1, AGES increased lapse risk among smokers randomized to placebo relative to those who received bupropion, suggesting that bupropion offsets increased propensity to lapse with higher AGES scores. Other pharmacogenetic investigations from these trials and others (including additional genetic markers combinations) have shown effects of genotype on smoking cessation in placebo groups (43, 56, 57). Bupropion is known to alter reuptake of synaptic dopamine (18). Hence, the significant AGES × drug effect enhances the biological plausibility that AGES might be a genetic marker of lapse risk in untreated smokers attempting to maintain abstinence rather than a proxy for some other non-biological environmentally-mediated process that may impact lapse (e.g., low socioeconomic status) (58).
