Initial responses to the first dose of nicotine in novel smokers: The role of exposure to environmental smoking and genetic predisposition

Background: Sensitivity to initial smoking constitutes an early predictor of the risk of dependence. We investigated the role of exposure to smoking (by parents, siblings, and peers) and reward-related candidate gene polymorphisms (OPRM1 A118G, DRD2 TaqlA and DRD4 bp VNTR) in adolescents' responses to initial smoking. Methods: We used cross-sectional survey data and saliva samples from 171 Dutch students who had never inhaled on a cigarette (mean age: 13.9 years). The outcome measure was adolescents' self-reported responses to initial smoking. Results: Exposure to peer smoking was associated with increased liking (OR = 1.74, CI = 1.13-2.70) and more pleasant sensations (beta = .21, p = .01). Exposure to maternal smoking was associated with less unpleasant sensations (beta = -.20, p = .01). Adolescents carrying the G-variant of the OPRM1 A118G polymorphism were more likely to report liking (OR = 2.50, CI = 1.09-5.73) and adolescents homozygous for the C-variant of the DRD2 TaqlA polymorphism reported less unpleasant sensations (beta = .18, p = .04). Conclusion: Although preliminary, these findings suggest that exposure to environmental smoking and polymorphisms in the OPRM1 and DRD2 gene may affect initial sensitivity to nicotine, an early phenotype of the risk of dependence. In the future, collaborative efforts to combine data from multiple studies in meta-analyses are needed to improve accuracy of estimated effects in genetic studies.