title: Gender-stratified gene and gene-treatment interactions in smoking cessation.
abstract: We conducted gender-stratified analyses on a systems-based candidate gene study of 53 regions involved in nicotinic response and the brain-reward pathway in two randomized clinical trials of smoking cessation treatments (placebo, bupropion, transdermal and nasal spray nicotine replacement therapy). We adjusted P-values for multiple correlated tests, and used a Bonferroni-corrected α-level of 5 × 10(-4) to determine system-wide significance. Four single-nucleotide polymorphisms (rs12021667, rs12027267, rs6702335, rs12039988; r2 > 0.98) in erythrocyte membrane protein band 4.1 (EPB41) had a significant male-specific marginal association with smoking abstinence (odds ratio (OR) = 0.5; 95% confidence interval (CI): 0.3-0.6) at end of treatment (adjusted P < 6 × 10(-5)). rs806365 in cannabinoid receptor 1 (CNR1) had a significant male-specific gene-treatment interaction at 6-month follow-up (adjusted P = 3.9 × 10(-5)); within males using nasal spray, rs806365 was associated with a decrease in odds of abstinence (OR = 0.04; 95% CI: 0.01-0.2). While the role of CNR1 in substance abuse has been well studied, we report EPB41 for the first time in the nicotine literature.
authors.affiliation: Department of Preventive Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lee
authors.forename: A W
authors.initials: AW
authors.lastname: Bergen
authors.forename: G E
authors.initials: GE
authors.lastname: Swan
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: C
authors.initials: C
authors.lastname: Lerman
authors.forename: D V
authors.initials: DV
authors.lastname: Conti
mesh_terms: D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012727:Sex Characteristics; D016540:Smoking Cessation
chemical_list: C571130:CNR1 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D043884:Receptor, Cannabinoid, CB1; C028841:erythrocyte membrane band 4.1 protein