Journal
PHARMACOGENOMICS
Volume 11, Issue 4, Pages 527-536Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.10.1
Keywords
bupropion; cohort study; dopamine D2 receptor; genetic; polymorphism; primary healthcare; smoking cessation
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Funding
- German Ministry of Education and Research [01EB0113]
- German Research Foundation [SPP 1226]
- National Genome Research Network (NGFN) of the German Federal Ministry of Education and Research (BMBF) NGFN plus [01GS08152]
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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.
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