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Nicotinic acetylcholine receptor variants are related to smoking habits, but not directly to COPD.

ABSTRACT: Genome-wide association studies identified single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine receptors (nAChRs) cluster as a risk factor for nicotine dependency and COPD. We investigated whether SNPs in the nAChR cluster are associated with smoking habits and lung function decline, and if these potential associations are independent of each other. The SNPs rs569207, rs1051730 and rs8034191 in the nAChR cluster were analyzed in the Vlagtwedde-Vlaardingen cohort (n = 1,390) that was followed for 25 years. We used GEE and LME models to analyze the associations of the SNPs with quitting or restarting smoking and with the annual FEV(1) decline respectively. Individuals homozygote (CC) for rs569207 were more likely to quit smoking (OR (95%CI) = 1.58 (1.05-2.38)) compared to wild-type (TT) individuals. Individuals homozygote (TT) for rs1051730 were less likely to quit smoking (0.64 (0.42; 0.97)) compared to wild-type (CC) individuals. None of the SNPs was significantly associated with the annual FEV(1) decline in smokers and ex-smokers. We show that SNPs in the nAChR region are associated with smoking habits such as quitting smoking, but have no significant effect on the annual FEV(1) decline in smokers and ex-smokers, suggesting a potential role of these SNPs in COPD development via smoking habits rather than via direct effects on lung function.

SUBMITTER: Budulac SE

PROVIDER: S-EPMC3305325 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Nicotinic acetylcholine receptor variants are related to smoking habits, but not directly to COPD.

Budulac Simona E SE Vonk Judith M JM Postma Dirkje S DS Siedlinski Mateusz M Timens Wim W Boezen Marike H MH

PloS one 20120315 3

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine receptors (nAChRs) cluster as a risk factor for nicotine dependency and COPD. We investigated whether SNPs in the nAChR cluster are associated with smoking habits and lung function decline, and if these potential associations are independent of each other. The SNPs rs569207, rs1051730 and rs8034191 in the nAChR cluster were analyzed in the Vlagtwedde-Vlaardingen cohort (n = 1,390) tha ...[more]

PMID: 22438921

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Project description:ImportanceCigarette smoking leads to upregulation of nicotinic acetylcholine receptors (nAChRs) in the human brain, including the common α4β2* nAChR subtype. While subjective aspects of tobacco dependence have been extensively examined as predictors of quitting smoking with treatment, no studies to our knowledge have yet reported the relationship between the extent of pretreatment upregulation of nAChRs and smoking cessation.ObjectiveTo determine whether the degree of nAChR upregulation in smokers predicts quitting with a standard course of treatment.Design, setting, and participantsEighty-one tobacco-dependent cigarette smokers (volunteer sample) underwent positron emission tomographic (PET) scanning of the brain with the radiotracer 2-FA followed by 10 weeks of double-blind, placebo-controlled treatment with nicotine patch (random assignment). Pretreatment specific binding volume of distribution (VS/fP) on PET images (a value that is proportional to α4β2* nAChR availability) was determined for 8 brain regions of interest, and participant-reported ratings of nicotine dependence, craving, and self-efficacy were collected. Relationships between these pretreatment measures, treatment type, and outcome were then determined. The study took place at academic PET and clinical research centers.Main outcomes and measuresPosttreatment quit status after treatment, defined as a participant report of 7 or more days of continuous abstinence and an exhaled carbon monoxide level of 3 ppm or less.ResultsSmokers with lower pretreatment VS/fP values (a potential marker of less severe nAChR upregulation) across all brain regions studied were more likely to quit smoking (multivariate analysis of covariance, F8,69 = 4.5; P < .001), regardless of treatment group assignment. Furthermore, pretreatment average VS/fP values provided additional predictive power for likelihood of quitting beyond the self-report measures (stepwise binary logistic regression, likelihood ratio χ21 = 19.8; P < .001).Conclusions and relevanceSmokers with less upregulation of available α4β2* nAChRs have a greater likelihood of quitting with treatment than smokers with more upregulation. In addition, the biological marker studied here provided additional predictive power beyond subjectively rated measures known to be associated with smoking cessation outcome. While the costly, time-consuming PET procedure used here is not likely to be used clinically, simpler methods for examining α4β2* nAChR upregulation could be tested and applied in the future to help determine which smokers need more intensive and/or lengthier treatment.Trial registrationclinicaltrials.gov Identifier: NCT01526005.

Dataset Information

Nicotinic acetylcholine receptor variants are related to smoking habits, but not directly to COPD.

Publications

Nicotinic acetylcholine receptor variants are related to smoking habits, but not directly to COPD.

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