Molecular Genetics of Successful Smoking Cessation

• DOI: 10.1001/archpsyc.65.6.683
• Publication Date: 2008-06-02T23:11:56Z
• Authors: George R. Uhl; Qing-Rong Liu; Tomas Drgon; Catherine Johnson; Donna Walther; Jed E. Rose; Sean P. David; Ray Niaura; Caryn Lerman
• Keywords: Bupropion; Nicotine replacement therapy; Genome-wide Association Study

<h3>Context</h3> Smoking remains a major public health problem. Twin studies indicate that the ability to quit smoking is substantially heritable, with genetics overlap modestly of vulnerability dependence on addictive substances. <h3>Objectives</h3> To identify replicated genes facilitate smokers' abilities achieve and sustain abstinence from (hereinafter referred as quit-success genes) found in more than 2 genome-wide association (GWA) successful vs unsuccessful abstainers, and, secondarily, nominate for selective involvement cessation success bupropion hydrochloride nicotine replacement therapy (NRT). <h3>Design</h3> The GWA results subjects 3 centers, secondary analyses NRT responders. <h3>Setting</h3> Outpatient trial participants centers. <h3>Participants</h3> European American smokers who successfully unsuccessfully abstain biochemical confirmation using NRT, bupropion, or placebo (N = 550). <h3>Main Outcome Measures</h3> Quit-success genes, reproducibly identified by clustered nominally positive single-nucleotide polymorphisms (SNPs) independent samples significant<i>P</i>values based Monte Carlo simulation trials. NRT-selective were nominated SNPs display much larger<i>t</i>values comparisons. bupropion-selective results. <h3>Results</h3> Variants are likely alter cell adhesion, enzymatic, transcriptional, structural, DNA, RNA, and/or protein-handling functions. unlikely represent chance observations (Monte Carlo<i>P</i>&lt; .0003). These modest substances memory. <h3>Conclusions</h3> support polygenic abstaining smoking, substance memory, gene variants influences therapeutic responses NRT. Molecular should help match types intensity antismoking treatments most benefit them.