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Nicotinic acetylcholine receptor {beta}2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.

Author(s): Conti DV, Lee W, Li D, Liu J, Van Den Berg D, Thomas PD, Bergen AW, Swan GE, Tyndale RF, Benowitz NL, Lerman C, for the Pharmacogenetics of Nicotine Addiction and Treatment Consortium

Affiliation(s): Department of Preventive Medicine, Keck School of Medicine, Zilkha Neurogenetics Institute, University of Southern California, Los Angeles, CA USA.

Publication date & source: 2008-07-01, Hum Mol Genet., [Epub ahead of print]

While 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 1,295 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. A SNP (rs2072661) in the 3' UTR region of the beta2 nicotinic acetylcholine receptor subunit (CHRNB2) has an impact on abstinence rates at 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 odds of quitting (OR = 0.31; 95% CI 0.18-0.55). Effect estimates indicate that treatment is more effective for individuals with the wild-type (OR = 2.14, 95% CI 1.20-3.81) compared to 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 (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.

Page last updated: 2008-08-11

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