title: Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.
abstract: Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated, there is substantial variability among individuals in treatment response. We performed a systems-based candidate gene study of 1295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled randomized clinical trial. Putative functional variants were supplemented with tagSNPs within each gene. We used global tests of main effects and treatment interactions, adjusting the P-values for multiple correlated tests. An SNP (rs2072661) in the 3' UTR region of the beta2 nicotinic acetylcholine receptor subunit (CHRNB2) has an impact on abstinence rates at the end of treatment (adjusted P = 0.01) and after a 6-month follow-up period (adjusted P = 0.0002). This latter P-value is also significant with adjustment for the number of genes tested. Independent of treatment at 6-month follow-up, individuals carrying the minor allele have substantially decreased the odds of quitting (OR = 0.31; 95% CI 0.18-0.55). Effect of estimates indicate that the treatment is more effective for individuals with the wild-type (OR = 2.14, 95% CI 1.20-3.81) compared with individuals carrying the minor allele (OR = 0.83, 95% CI 0.32-2.19), although this difference is only suggestive (P = 0.10). Furthermore, this SNP demonstrated a role in the time to relapse (P = 0.0002) and an impact on withdrawal symptoms at target quit date (TQD) (P = 0.0009). Overall, while our results indicate strong evidence for CHRNB2 in ability to quit smoking, these results require replication in an independent sample.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, Zilkha Neurogenetics Institute, University of Southern California, 1501 San Pablo Street, ZNI 445, Los Angeles, CA 90089, USA. dconti@usc.edu
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: Won
authors.initials: W
authors.lastname: Lee
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thomas
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
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
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012008:Recurrence; D012907:Smoking / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D016540:Smoking Cessation / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000523:psychology / Q000628:therapy; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D044465:White People / Q000235:genetics / Q000523:psychology
chemical_list: D020413:3' Untranslated Regions; D011978:Receptors, Nicotinic