title: SNPs within CHRNA5-A3-B4 and CYP2A6/B6 are associated with smoking dependence but not with tobacco dependence treatment outcomes in the Czech population.
abstract: OBJECTIVE
  Tobacco/nicotine dependence has a significant heritable component. Genome-wide association studies have associated the single nucleotide polymorphisms (SNPs) rs578776, rs16969968, rs6474412, rs3733829 and rs4105144 with nicotine dependence in Western European populations. We examined whether these SNPs influence nicotine dependence and successful treatment of tobacco dependence in the Czech middle-European population.
  
  
  METHODS
  Variants were analysed by PCR-RFLP or by TaqMan assay in 807 adult heavy tobacco-dependent smokers - patients of the Centre for Treatment of Tobacco Dependence (Prague) as well as 1,362 self-reported non-smokers.
  
  
  CONCLUSIONS
  Except for rs3733829, association with tobacco dependence was confirmed for all other genetic variants. In agreement with previous studies, the strongest determinant of tobacco dependence was rs16969968 with OR (95%CI) 1.32 (1.08-1.62) for A allele carriers vs. GG comparison (P=0.003). In contrast, none of the analysed variants reached significance with respect to a 1-year course of successful tobacco dependence treatment (all P over 0.18) in a subset of 525 patients.
  
  
  CONCLUSIONS
  We confirmed the association between variants within genes that code nicotinic-acetylcholine receptors (-A3, -A5 and -B3), CYP2A6/B6 and tobacco dependence development in the Czech population. The success of the tobacco dependence treatment was not influenced by the analysed SNPs.
authors.affiliation: Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: jahb@ikem.cz.
authors.forename: J A
authors.initials: JA
authors.lastname: Hubacek
authors.affiliation: Centre for Tobacco-Dependent, 3(rd) Department of Medicine - Department of Endocrinology and Metabolism, 1(st) Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic; Institute of Hygiene and Epidemiology, 1(st) Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Pankova
authors.affiliation: Centre for Tobacco-Dependent, 3(rd) Department of Medicine - Department of Endocrinology and Metabolism, 1(st) Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Stepankova
authors.affiliation: Centre for Tobacco-Dependent, 3(rd) Department of Medicine - Department of Endocrinology and Metabolism, 1(st) Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Zvolska
authors.affiliation: Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Adamkova
authors.affiliation: Statistical Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Lanska
authors.affiliation: Centre for Tobacco-Dependent, 3(rd) Department of Medicine - Department of Endocrinology and Metabolism, 1(st) Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic; Institute of Hygiene and Epidemiology, 1(st) Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Kralikova
mesh_terms: D000328:Adult; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics; D003604:Czechoslovakia; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000628:therapy*
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6
keywords: CYP2A6/B6; Czechs; EGLN2; Nicotine-acetylcholine receptors; Smoking cessation; Tobacco dependence