title: Variant within the promoter region of the CHRNA3 gene associated with FTN dependence is not related to self-reported willingness to quit smoking.
abstract: BACKGROUND
  Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region is robustly associated with smoking quantity. Conversely, the association between one of the most significant single nucleotide polymorphisms (SNPs; rs1051730 within the CHRNA3 gene) with perceived difficulty or willingness to quit smoking among current smokers is unknown.
  
  
  METHODS
  Cross-sectional study including current smokers, 502 women, and 552 men. Heaviness of smoking index (HSI), difficulty, attempting, and intention to quit smoking were assessed by questionnaire.
  
  
  RESULTS
  The rs1051730 SNP was associated with increased HSI (age, gender, and education-adjusted mean ± SE: 2.6 ± 0.1, 2.2 ± 0.1, and 2.0 ± 0.1 for AA, AG, and GG genotypes, respectively, p < .01). Multivariate logistic regression adjusting for gender, age, education, leisure-time physical activity, and personal history of cardiovascular or lung disease showed rs1051730 to be associated with higher smoking dependence (odds ratio [OR] and 95% CI for each additional A-allele: 1.38 [1.11-1.72] for smoking more than 20 cigarette equivalents/day; 1.31 [1.00-1.71] for an HSI ≥5 and 1.32 [1.05-1.65] for smoking 5 min after waking up) and borderline associated with difficulty to quit (OR = 1.29 [0.98-1.70]), but this relationship was no longer significant after adjusting for nicotine dependence. Also, no relationship was found with willingness (OR = 1.03 [0.85-1.26]), attempt (OR = 1.00 [0.83-1.20]), or preparation (OR = 0.95 [0.38-2.38]) to quit. Similar findings were obtained for other SNPs, but their effect on nicotine dependence was no longer significant after adjusting for rs1051730.
  
  
  CONCLUSIONS
  These data confirm the effect of rs1051730 on nicotine dependence but failed to find any relationship with difficulty, willingness, and motivation to quit.
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland. pedro-manuel.marques-vidal@chuv.ch
authors.forename: Pedro
authors.initials: P
authors.lastname: Marques-Vidal
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Fred
authors.initials: F
authors.lastname: Paccaud
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Jacques
authors.initials: J
authors.lastname: Cornuz
mesh_terms: D000328:Adult; D002884:Chromosomes, Human, Pair 15; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation / Q000523:psychology; D011795:Surveys and Questionnaires; D013557:Switzerland; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic