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Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome.

ABSTRACT: Genetic influences on smoking cessation treatment outcome may be affected by pretreatment patient characteristics. Nicotine dependence is arguably the most salient clinical factor in smoking cessation.In this secondary analysis of clinical trial data (N=793), we examined nicotine dependence severity as a moderator of the effects of 1198 single nucleotide polymorphisms (SNPs) in 53 biologically-relevant gene regions on smoking cessation outcomes. P-values were adjusted to account for multiple correlated SNPs within a gene region; corrected system-wide significance was 5 × 10(-4).SNP × nicotine dependence interactions reached region-wide significance for several SNPs in the Dopamine Beta Hydroxylase (DBH) locus (0.0005

SUBMITTER: Leventhal AM

PROVIDER: S-EPMC4095777 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome.

Leventhal Adam M AM Lee Wonho W Bergen Andrew W AW Swan Gary E GE Tyndale Rachel F RF Lerman Caryn C Conti David V DV

Drug and alcohol dependence 20140305

<h4>Background</h4>Genetic influences on smoking cessation treatment outcome may be affected by pretreatment patient characteristics. Nicotine dependence is arguably the most salient clinical factor in smoking cessation.<h4>Methods</h4>In this secondary analysis of clinical trial data (N=793), we examined nicotine dependence severity as a moderator of the effects of 1198 single nucleotide polymorphisms (SNPs) in 53 biologically-relevant gene regions on smoking cessation outcomes. P-values were a ...[more]

PMID: 24667010

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Project description:IntroductionGenetic variation in Cytochrome P450 2A6 (CYP2A6), the major nicotine metabolizing enzyme, is associated with nicotine dependence and smoking cessation. Nicotine dependence severity also predicts smoking cessation. Our goals were to determine how CYP2A6 variation and nicotine dependence alter smoking cessation, and whether dependence could refine CYP2A6-based treatment recommendations.Aims and methodsAdult smokers treated for 12 weeks with placebo, nicotine patch, or varenicline (NCT01314001) were grouped as CYP2A6 normal (n = 567) or slow (n = 432) nicotine metabolizers based on a CYP2A6 weighted genetic risk score. Fagerström test for nicotine dependence scores were measured at baseline and biochemically verified smoking cessation was assessed at end of treatment.ResultsDependence neither mediated nor moderated an association between CYP2A6 variation and smoking cessation overall, within any treatment arm, or after stratifying by ancestry (n = 591 European, n = 408 African ancestry) or sex (n = 444 women, n = 555 men). In within-treatment analyses, the mediation effect odds ratio (OR) ranged from 0.95 to 1.00 and the bias-corrected 95% confidence interval contained 1. Moderation (i.e. interaction) effect ORs ranged from 0.88 to 1.61 (p = .397-.828). For CYP2A6 normal metabolizers, quit rates on varenicline were similar for those with high (41.1%) and low (43.4%) dependence, while quit rates were lower for those with high versus low dependence on both patch (16.5 vs. 29.7%) and placebo (8.9 vs. 18.5%). CYP2A6 slow metabolizers with high versus low dependence had lower quit rates in all three treatment arms.ConclusionsAlthough nicotine dependence severity neither mediated nor moderated CYP2A6 associations with smoking cessation, incorporating information on dependence may optimize the choice of smoking cessation treatment aid in CYP2A6 normal and slow metabolizers.ImplicationsVariation in CYP2A6 and nicotine dependence severity alter smoking cessation success. Our findings suggest that while nicotine dependence severity is unlikely to mediate or moderate CYP2A6 associations with cessation, incorporating patient information on both CYP2A6 and nicotine dependence severity may lead to improved smoking cessation strategies.

Project description:IntroductionThe number of cigarettes smoked per day (CPD) is a component of commonly used nicotine dependence measures and often used as a smoking cessation treatment outcome. Yet relighting (ie, smoking used cigarette butts) is not usually considered when CPD is assessed, which may underestimate nicotine dependence and result in an inaccurate picture of smoking behaviors.Aims and methodsData from a randomized controlled trial of a smoking cessation intervention were used. Fagerström Test for Cigarette Dependence (FTCD), CPD, and the frequency of smoking (number of smoking episodes/day) assessed at baseline and 3-month follow-up were used.ResultsParticipants were 49 adults with mood disorders who smoke daily receiving outpatient psychiatric treatment. At baseline, 27 (55.1%) participants reported relighting cigarettes, and 6 (27.3%) of those who did not report relighting at baseline reported relighting at 3-month follow-up. Replacing CPD with the frequency of smoking to recalculate the total FTCD score increased the score for 21 participants (43%). The mean FTCD scores increased from 4.61 to 5.16, from a classification of low to medium dependence, and 16 participants (33%) moved up in the dependence classification. Of the 31 participants who reported a >=50% reduction in CPD at 3-month follow-up, 5 (16%) did not achieve the outcome of >=50% reduction in the frequency of smoking per day.ConclusionsIn this sample of adults with mood disorders who smoke, over half reported relighting cigarettes. Results underscore the importance of incorporating the frequency of smoking/relighting when assessing nicotine dependence and patterns of smoking behaviors in high-risk populations.ImplicationsThis is the first study to investigate the patterns of relighting behavior and its impact on nicotine dependence and smoking cessation treatment outcome measures among treatment-seeking adults with mood disorders who smoke. The majority were relighting, and over a quarter of those who did not report relighting at baseline subsequently reported relighting in the context of a quit attempt. The findings demonstrate that overlooking relighting may underestimate nicotine dependence and overestimate the rates of those who have made meaningful changes in smoking behavior. Incorporating the frequency of smoking/relighting may help to more accurately capture nicotine dependence and patterns of smoking behavior among high-risk populations.

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Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome.

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Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome.

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