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DRD1 associations with smoking abstinence across slow and normal nicotine metabolizers.


ABSTRACT: Nicotine metabolism and genetic variation have an impact on nicotine addiction and smoking abstinence; however, further research is required. The nicotine metabolite ratio (NMR) is a robust biomarker of nicotine metabolism used to categorize slow and normal nicotine metabolizers (lower 25th quartile cut off). In two randomized clinical trials of smoking abstinence treatments, we conducted NMR-stratified analyses on smoking abstinence across 13 regions coding for nicotinic acetylcholine receptors and proteins involved in the dopamine reward system. Gene×NMR interaction P-values were adjusted for multiple correlated tests, and we used a Bonferroni-corrected ?-level of 0.004 to determine system-wide significance. Three single-nucleotide polymorphisms in DRD1 (rs11746641, rs2168631, and rs11749035) had significant interactions (0.001 ? adjusted P-values ? 0.004) with increased odds of abstinence within slow metabolizers (odds ratios=3.1-3.5, 95% confidence interval 1.7-6.7). Our findings support the role of DRD1 in nicotine dependence, and identify genetic and nicotine metabolism profiles that may interact to impact nicotine dependence.

PROVIDER: S-EPMC3376177 | BioStudies |

REPOSITORIES: biostudies

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