title: 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.
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Simona E
authors.initials: SE
authors.lastname: Budulac
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Mateusz
authors.initials: M
authors.lastname: Siedlinski
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Marike H
authors.initials: MH
authors.lastname: Boezen
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D016540:Smoking Cessation; D014029:Tobacco Use Disorder / Q000235:genetics
chemical_list: D011978:Receptors, Nicotinic