The α5 nAChR subunit mediates an inhibitory effect of nicotine on brain reward systems (27). Mice with lower α5 nAChR function exhibited increased nicotine intake (27). Since rs2036527 was previously associated with increased nicotine intake in African Americans (21), it is likely that rs2036527 (or SNPs in high linkage disequilibrium) results in lower α5 nAChR function. Both nicotine gum and bupropion could have inhibitory effects on nicotine reward since both of them can bind to the nAChR (28, 29). The inhibitory effects of nicotine gum and bupropion may be weaker in individuals with rs2036527 (due to their lower α5 function), reducing the efficacy of these treatments.
