Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch

Polymorphisms in the dopamine D-2 receptor ((32806)DRD2 C/T and (22316)DRD2 A/G) and in dopamine beta hydroxylase ((1368)DBHA/G) have been implicated in modulation of smoking and other reward-seeking behaviours. We hypothesized that these alleles would predict the outcome of nicotine patch therapy for smoking cessation. In 1991-93, we performed a randomized controlled trial of the nicotine patch on 1686 heavy smokers (greater than or equal to 15 cigarettes/day). In 1999-2000, we contacted 1532 of the 1612 subjects still available; 767 (50%) completed a questionnaire and gave a blood sample. In the 755 cases in which DNA was successfully genotyped, we examined associations between the polymorphisms in DRD2 and DBH, and smoking cessation. At 1 week, the patch was more effective for smokers with (32806)DRD2 CT/TT genotype [patch/placebo odds ratio (OR) 2.8,95% confidence interval (CO 1.7-4.61 than with CC (OR 1.4, 0.9-2.1; P for difference in ORs 0.04). Smokers with both (32806)DRD2 CT/TT and (DBH)-D-1368 GA/AA genotypes had an OR of 3.6 (2.0-6.5) compared to 1.4 (1.0-2.1) for others (P = 0.01). At 12 weeks, the ORs for these genotypic groups were 3.6 (1.7-7.8) and 1.4 (0.9-2.3), respectively (P = 0.04). There was no association between patch effectiveness and (22316)DRD2 exon 8. Short-term effectiveness of the nicotine patch may be related to dopamine beta-hydroxylase and dopamine D2 receptor genotype. Our results support the need for further investigation into personalized therapies for smoking cessation based on individual genotype.