Prospective Association of Dopamine-Related Polymorphisms with Smoking Cessation in General Care

Abstract

Aims: Genetic contributions to nicotine dependence have been demonstrated repeatedly, but the relevance of individual polymorphisms for smoking cessation remains controversial. Materials & methods: We examined genotypes at two dopamine-related loci, DRD2/ANKK1 (rs1800497) and DBH (rs77905), in 577 heavy smokers participating in a prospective study of smoking cessation in general care in Germany. Results: Smoking status after 1 year was significantly associated with DRD2/ANKK1, odds of abstinence being 4.4-fold (95% CI: 1.5–12.9) increased in TT- versus CC-homozygous subjects (p = 0.008). No effect was observed for the DBH genotype. The smoking cessation drug bupropion appeared to be particularly effective in CC-homozygotes (among CC subjects there was a 28% higher cessation probability among those taking buproprion; among T carrier subjects there was an increase only by 12%). Conclusion: The large effects observed for DRD2/ANKK1 might be related to our study design, in which individual therapy was decided by the physician. Further studies are needed to clarify the genetic effects of DRD2/ANKK1 especially in ‘real-life‘ settings outside clinical trials.

KEYWORDS::

• bupropion
• cohort study
• dopamine D2 receptor
• genetic polymorphism
• primary healthcare
• smoking cessation

Acknowledgments

We express our gratitude to the patients and physicians contributing to this study. Isabel Lerch was an essential help with data acquisition, Andrea Pfister, Marina Füg and Christine Hohmeyer with genotyping and DNA extraction. Constructive contributions from Professor Marcella Rietschel, which substantially improved the manuscript.

Financial & competing interests disclosure

The authors declare that this work was funded by the German Ministry of Education and Research within the context of the Baden–Württemberg Research Network on Addiction (project number 01EB0113) and in part by a grant within the German Research Foundation Priority Programme ‘Nicotine‘ (SPP 1226). This work was furthermore supported by a grant from the National Genome Research Network (NGFN) of the German Federal Ministry of Education and Research (BMBF) NGFN plus (01GS08152). 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 authors declare that this work was funded by the German Ministry of Education and Research within the context of the Baden–Württemberg Research Network on Addiction (project number 01EB0113) and in part by a grant within the German Research Foundation Priority Programme ‘Nicotine‘ (SPP 1226). This work was furthermore supported by a grant from the National Genome Research Network (NGFN) of the German Federal Ministry of Education and Research (BMBF) NGFN plus (01GS08152). 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.