title: Associations of nicotine intake measures with CHRN genes in Finnish smokers.
abstract: BACKGROUND
  Genetic effects contribute to individual differences in smoking behavior. Persistence to smoke despite known harmful health effects is mostly driven by nicotine addiction. As the physiological effects of nicotine are mediated by nicotinic acetylcholine receptors (nAChRs), we aimed at examining whether single nucleotide polymorphisms (SNPs) residing in nAChR subunit (CHRN) genes, other than CHRNA3/CHRNA5/CHRNB4 gene cluster previously showing association in our sample, are associated with smoking quantity or serum cotinine levels.
  
  
  METHODS
  The study sample consisted of 485 Finnish adult daily smokers (age 30-75 years, 59% men) assessed for the number of cigarettes smoked per day (CPD) and serum cotinine level. We first studied SNPs residing on selected nAChR subunit genes (CHRNA2, CHRNA4, CHRNA6/CHRNB3, CHRNA7, CHRNA9, CHRNA10, CHRNB2, CHRNG/CHRND) genotyped within a genome-wide association study for single SNP and multiple SNP associations by ordinal regression. Next, we explored individual haplotype associations using sliding window technique.
  
  
  RESULTS
  At one of the 8 loci studied, CHRNG/CHRND (chr2), single SNP (rs1190452), multiple SNP, and 2-SNP haplotype analyses (SNPs rs4973539-rs1190452) all showed statistically significant association with cotinine level. The median cotinine levels varied between the 2-SNP haplotypes from 220 ng/ml (AA haplotype) to 249 ng/ml (AG haplotype). We did not observe significant associations with CPD.
  
  
  CONCLUSIONS
  These results provide further evidence that the γ-δ nAChR subunit gene region is associated with cotinine levels but not with the number of CPD, illustrating the usefulness of biomarkers in genetic analyses.
authors.affiliation: Department of Public Health, University of Helsinki, Mannerheimintie 172, Helsinki, Finland.
authors.forename: Kaisu
authors.initials: K
authors.lastname: Keskitalo-Vuokko
authors.forename: Janne
authors.initials: J
authors.lastname: Pitkäniemi
authors.forename: Ulla
authors.initials: U
authors.lastname: Broms
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.forename: Arpo
authors.initials: A
authors.lastname: Aromaa
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Outi
authors.initials: O
authors.lastname: Salminen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Anu
authors.initials: A
authors.lastname: Loukola
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic