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Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.

ABSTRACT: Few studies have sought to identify specific genetic markers associated with cigarettes per day (CPD) during adolescence and young adulthood, the period of greatest vulnerability for the development of nicotine dependence.We used a longitudinal design to investigate the effect of neuronal nicotinic acetylcholine receptor (CHRN) subunit genes on CPD from 15 to 21 years of age in young smokers of European descent (N = 439, 59% female). The number of CPD typically smoked during the previous 30 days was self-reported. Single nucleotide polymorphisms (SNPs) from CHRN genes were genotyped using DNA extracted from saliva samples collected at the 5-year assessment. Mixed-model analyses of SNP effects were computed across age at the time of assessment using log-transformed CPD as the phenotype. Data from the 1000 Genomes Project were used to clarify the architecture of CHRN genes to inform SNP selection and interpretation of results.CPD was associated with a CHRNB3A6 region tagged by rs2304297, with CHRNA5A3B4 haplotype C (tagged by rs569207), and with the CHRNA2 SNP rs2271920, ps < .004. The reliability of single-SNP associations was supported by the correspondence between a more extensive set of SNP signals and the underlying genetic architecture. The 3 signals identified in this study appear to make independent contributions to CPD, and their combined effect accounts for 5.5% of the variance in log-transformed CPD.Level of CPD during adolescence and young adulthood is associated with CHRNB3A6, CHRNA5A3B4, and CHRNA2.

SUBMITTER: Cannon DS

PROVIDER: S-EPMC3880230 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.

Cannon Dale S DS Mermelstein Robin J RJ Hedeker Donald D Coon Hilary H Cook Edwin H EH McMahon William M WM Hamil Cindy C Dunn Diane D Weiss Robert B RB

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20130813 2

<h4>Introduction</h4>Few studies have sought to identify specific genetic markers associated with cigarettes per day (CPD) during adolescence and young adulthood, the period of greatest vulnerability for the development of nicotine dependence.<h4>Methods</h4>We used a longitudinal design to investigate the effect of neuronal nicotinic acetylcholine receptor (CHRN) subunit genes on CPD from 15 to 21 years of age in young smokers of European descent (N = 439, 59% female). The number of CPD typical ...[more]

PMID: 23943838

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Project description:IntroductionTo examine whether changes in select measures of e-cigarette puffing topography are associated with changes in smoking behavior.MethodsSixteen current cigarette smokers were instructed to completely switch from smoking combustible cigarettes to using e-cigarettes over a 2-week period. The study was completed in the Southern Midwestern region of the United States. Measures included demographics, smoking history, and cigarette dependence, as well as baseline and 2-week follow-up self-reported cigarettes per day, cigarette craving and urges, exhaled carbon monoxide readings, and e-cigarette usage data (puff number, puffing time, and average puff duration) collected via the e-cigarette built-in puff counter.ResultsOver the 2-week switching period, participants significantly reduced their cigarettes per day (~80% reduction, p < .0001). Although the number of e-cigarette puffs/day remained relatively stable (p > .05), the average total e-cigarette daily puffing time increased significantly (p = .001). Users' average puff duration increased by 91 ms/puff/d (p < .001). The percentage decrease in cigarettes smoked per day was significantly and directly related to the slope of subjects' average puff duration over time (r(13) = .62, p = .01), such that as cigarettes per day decreased, puff duration increased. Self-reported smoking urges remained relatively stable from baseline to the end of the 2-week period (p > .05).ConclusionsAmong smokers switching to an e-cigarette, greater increases in e-cigarette puff duration was associated with greater reductions in cigarette smoking.ImplicationsThe current study is one of the first to examine changes in smokers' e-cigarette puffing behavior and associated changes in cigarette consumption as they attempt to completely switch to e-cigarettes. During a 2-week switching period, participants reduced their cigarettes per day. Moreover, although e-cigarette puffs per day remained relatively stable, users' average puff duration increased significantly. Greater increases in e-cigarette puff duration were associated with greater reductions in cigarette smoking. Understanding how to effectively use an e-cigarette to best reduce and eventually quit smoking will be necessary as smokers increasingly turn to these products to facilitate possible cessation.

Project description:RationaleThe CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported smoking behavior and also harbors the strongest genetic associations with chronic obstructive pulmonary disease (COPD) and lung cancer. Because the associations with lung disease remain after adjustment for self-reported smoking behaviors, it has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung cancer susceptibility independently of their effects on smoking.ObjectivesTo compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of current cigarette exposure, with self-reported smoking behaviors.MethodsA total of 1,521 European American and 247 African American current smokers recruited into smoking cessation studies were assessed for CO at intake before smoking cessation. DNA samples were genotyped using the Illumina Omni2.5 microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked per day, Fagerstrom test for nicotine dependence) were studied.Measurements and main resultsVariants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a nonsynonymous variant in CHRNA5, are genomewide association study-significantly associated with CO (β = 2.66; 95% confidence interval [CI], 1.74-3.58; P = 1.65 × 10(-8)), and this association remains strong after adjusting for smoking behavior (β = 2.18; 95% CI, 1.32-3.04; P = 7.47 × 10(-7)). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 × 10(-4)) in African Americans (r = 0.14; 95% CI, 0.02-0.26; P = 0.003) than in European-Americans (r = 0.36; 95% CI, 0.31-0.40; P = 0.0001).ConclusionsExhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.

Dataset Information

Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.

Publications

Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.

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