Abstract
BackgroundGenetic influences on smoking cessation treatment outcome may be affected by pretreatment patient characteristics. Nicotine dependence is arguably the most salient clinical factor in smoking cessation. Methods: In this secondary analysis of clinical trial data (N=793), we examined nicotine dependence severity as a moderator of the effects of 1198 single nucleotide polymorphisms (SNPs) in 53 biologically-relevant gene regions on smoking cessation outcomes. P-values were adjusted to account for multiple correlated SNPs within a gene region; corrected system-wide significance was 5×10−4. Results: SNP×nicotine dependence interactions reached region-wide significance for several SNPs in the Dopamine Beta Hydroxylase (DBH) locus (0.0005<Adjusted-P<0.05), including rs1541333, which reached system-wide significance for predicting end of treatment (EOT) abstinence (Adjusted-P=0.0004). A haplotype including 6 DBH SNPs predicted abstinence at EOT (OR=1.7, P=0.001) and 6-month follow-up (OR=1.6, P=0.008) in those with high nicotine dependence (n=526) but not in those with low dependence (n=227). The DBH signal observed here may be distinct from a previously reported genome-wide significant signal for former smoking status and from the principal haplotype associated with plasma dopamine beta-hydroxylase activity. A haplotype within the Chromosome 15 Nicotinic Acetylcholine Receptor gene region predicted abstinence at EOT in those with high (OR=2.0, P=0.0004) but not low (P=0.6) dependence in post hoc analyses. Conclusions: Considering pre-treatment nicotine dependence level may optimize the prediction of genetic influences on cessation outcomes. If replicated, results like these may inform prognosticative genomic screening panels designed to identify smokers at high risk of relapse when coupled with severe nicotine dependence.
Accepted Version (Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.