title: Smoking cessation and variations in nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 genes.
abstract: BACKGROUND
  Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation.
  
  
  METHODS
  Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who reported regularly smoking more than 20 cigarettes at some point in their lives.
  
  
  RESULTS
  Given the genotype distributions and number of cessation events observed, the power to detect associations ranged from 54% to 97% for hazard ratios of 1.2 to 1.4 in case of the variant with strongest prior evidence (alpha = .05). Nonetheless, neither individual polymorphisms nor inferred multilocus haplotypes were significantly associated with smoking cessation.
  
  
  CONCLUSIONS
  Although the robust association of the nicotinic acetylcholine receptor subunit genes investigated with smoking-related phenotypes is an apparent success story of genetic epidemiology, the respective variations seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. L.Breitling@DKFZ-Heidelberg.de.
authors.forename: Lutz Philipp
authors.initials: LP
authors.lastname: Breitling
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.forename: Kirstin
authors.initials: K
authors.lastname: Mittelstrass
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Elke
authors.initials: E
authors.lastname: Raum
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D016540:Smoking Cessation
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human