Genetic Variation in Three Candidate Genes and Nicotine Dependence, Withdrawal and Smoking Cessation in Hospitalized Patients

Abstract

Aims: This study evaluates the relationship of six polymorphisms found in the CHRNA3, DRD2 and COMT genes with nicotine dependence, the ability to quit smoking and the occurrence of withdrawal symptoms after short-term use of nicotine patch in hospitalized patients. Materials & methods: The study included 233 participants from a double-blind, placebo-controlled trial of nicotine patch substitution with a 6-month follow-up period. Nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence (FTND) questionnaire, withdrawal symptoms by the Minnesota Nicotine Withdrawal Scale questionnaire and smoking cessation by self-reported abstinence at 1 week, 1 month and 6 months after treatment. Results: After correcting for multiple testing, three polymorphisms in the DRD2 gene (Taq1A, Taq1B and Pro319Pro) were significantly associated with nicotine dependence (p = 0.018, p = 0.048 and p = 0.006, respectively). Using a cutoff point for the FTND score, the CHRNA3 Tyr215Tyr (rs1051730) polymorphism was also associated with nicotine dependence (p = 0.037 and p = 0.074 after correction for multiple testing). No association of any of the studied polymorphisms was observed with either smoking cessation or the occurrence of withdrawal symptoms. Conclusion: This study confirms the reported association of the CHRNA3 locus with nicotine dependence and shows the involvement of two independent DRD2 polymorphisms in nicotine dependence.

KEYWORDS::

• CHRNA3
• COMT
• DRD2
• nicotine dependence
• polymorphism
• smoking cessation
• withdrawal

Acknowledgements

We wish to thank all the participants and data nurses/managers in this study. Special thanks to Dr Elaine Johnstone for delivering the primer sequences for the control gene. Thanks are also expressed to Virginie de Gelder and Sofie De Langhe for their help with the genotyping work. Furthermore, we also gratefully acknowledge the contribution of Dr Georges Van Maele for his help with the data collection and statistics and to Dr Hedwig Boudrez for the study set up.

Financial & competing interests disclosure

The Withdrawal Intervention by Nicotine Substitution Therapy in hospitalized smokers (WINST) study was conducted through a grant of the Foundation of Scientific Research (FWO number G.0604.06), kindly provided by the Vlaamse Liga tegen Kanker through their smoking cessation campaign ‘Kom Op Tegen Kanker 2005‘. The WINST study was further made possible by an independent research grant from McNeil AB, Helsingborg, Sweden. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The Withdrawal Intervention by Nicotine Substitution Therapy in hospitalized smokers (WINST) study was conducted through a grant of the Foundation of Scientific Research (FWO number G.0604.06), kindly provided by the Vlaamse Liga tegen Kanker through their smoking cessation campaign ‘Kom Op Tegen Kanker 2005‘. The WINST study was further made possible by an independent research grant from McNeil AB, Helsingborg, Sweden. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.