Evaluate nicotinic acetycholine receptor (nAChR) single nucleotide polymorphism (SNP) association with seven day point prevalence abstinence (abstinence) in randomized clinical trials of smoking cessation therapies (RCTs) in individuals grouped by pharmacotherapy randomization to inform the development of personalized smoking cessation therapy.
We quantified association of four SNPs at three nAChRs with abstinence in eight RCTs. Participants were 2,633 outpatient treatment-seeking, self-identified European ancestry individuals smoking ≥10 cigarettes per day, recruited via advertisement, prescribed pharmacotherapy, and provided with behavioral therapy. Interventions included nicotine replacement therapy (NRT), bupropion, varenicline, placebo or combined NRT and bupropion, and five modes of group and individual behavioral therapy. Outcome measures tested in multivariate logistic regression were end of treatment (EOT) and six month (6MO) abstinence, with demographic, behavioral and genetic covariates.
“Risk” alleles previously associated with smoking heaviness were significantly (P<0.05) associated with reduced abstinence in the placebo pharmacotherapy group (PG) at 6MO [for rs588765 OR (95%CI) 0.41 (0.17–0.99)], and at EOT and at 6MO [for rs1051730, 0.42 (0.19–0.93) and 0.31 (0.12–0.80)], and with increased abstinence in the NRT PG at 6MO [for rs588765 2.07 (1.11–3.87) and for rs1051730 2.54 (1.29–4.99)]. We observed significant heterogeneity in rs1051730 effects (F=2.48, P=0.021) between PGs.
chr15q25.1 nAChR SNP risk alleles for smoking heaviness significantly increase relapse with placebo treatment and significantly increase abstinence with NRT. These SNP-PG associations require replication in independent samples for validation, and testing in larger sample sizes to evaluate whether similar effects occur in other PGs.