Abstract

Nicotine metabolism and genetic variation have an impact on nicotine addiction and smoking abstinence; however, further research is required. The nicotine metabolite ratio is a robust biomarker of nicotine metabolism used to categorize slow and normal nicotine metabolizers. 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 α-level of 0.004 to determine system-wide significance. Three single-nucleotide polymorphisms in DRD1 had significant interactions with increased odds of abstinence within slow metabolizers. Our findings support the role of DRD1 in nicotine dependence, and identify genetic and nicotine metabolism profiles that may interact to impact nicotine dependence. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.