While independent replication will ultimately be required, the results of the present study may have important implications for the treatment of nicotine dependence. We found strong and consistent evidence for the association of two CHRNB2 3′ UTR SNPs with multiple phenotypes assessed in the current trial, including abstinence at both EOT and 6-month follow-up, days to relapse, and nicotine withdrawal symptoms. While the literature provides four independent examples of the lack of association of these two CHRNB2 SNPs with nicotine dependence, these SNPs may be robust markers for identifying smokers most likely to relapse and those who may benefit from bupropion therapy. In addition, these SNPs should be examined within pharmacogenetic studies of varenicline, a new α4β2 nAChR partial agonist medication for smoking cessation. Future studies should also extend molecular genetic analysis to include the large 3′ UTR of CHRNB2 (39) and a novel set of nAChR-interacting proteins that regulate β2 nAChR signaling (62). For example, the 3′ UTR of CHRNB2, extends some 4 kb 3′ of the coding region, and contains seven predicted human micro-RNA targets, including a target for human miR-432 located 13 base pairs 5′ of rs2072660 (63).
