title: 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 α-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.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, USA.
authors.forename: Wonho
authors.initials: W
authors.lastname: Lee
authors.forename: Riju
authors.initials: R
authors.lastname: Ray
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.forename: Paul
authors.initials: P
authors.lastname: Thomas
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
mesh_terms: D000328:Adult; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D012907:Smoking; D016540:Smoking Cessation; D014029:Tobacco Use Disorder
chemical_list: D017447:Receptors, Dopamine D1; D009538:Nicotine