title: Possible association of nicotinic acetylcholine receptor gene (CHRNA4 and CHRNB2) polymorphisms with nicotine dependence in Japanese males: an exploratory study.
abstract: BACKGROUND
  Smoking is a leading global cause of avoidable mortality. It has been reported that the nicotinic acetylcholine receptor (CHRNA4 and CHRNB2) genes might be associated with smoking behavior in several ethnic populations. However, no study between the 2 genes and nicotine dependence (ND) using a Japanese population has been reported.
  
  
  METHODS
  We examined the association between ND and 5 single nucleotide polymorphisms (SNPs) within the CHRNA4 and 3 SNPs within the CHRNB2 using a well characterized sample of 558 Japanese healthy male workers with a relatively homogeneous background. The Fagerström test for nicotine dependence (FTND) was used to quantify the degree of ND. Additionally, we explored the effect of gene-gene interactions of the 2 genes on ND.
  
  
  RESULTS
  We found CHRNB2 rs4845652 genotypes to be associated with FTND scores under an additive genetic model: rs4845652 T-allele carriers had lower ND levels (p=0.038; when adjusted for smoking duration: p=0.052). Furthermore, we demonstrated a possible gene-gene interaction of CHRNA4 and CHRNB2 on ND in a dose-dependent manner: those smokers with CHRNA4 rs1044397 GG or GA genotypes along with CHRNB2 rs4845652 CC genotype are likely to demonstrate higher ND scores.
  
  
  CONCLUSIONS
  These findings suggest that CHRNB2 rs4845652 T-allele carriers may be associated with lower levels of ND, and that certain allelic combinations of CHRNA4 and CHRNB2 might be correlated with higher ND levels. This preliminary study has certain limitations (issues such as sample size/power and multiple testing) that need to be taken into account, and the present work thus has an experimental nature.
authors.affiliation: Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: H-I
authors.initials: HI
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Shinkai
authors.forename: K
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Sakata
authors.forename: Y
authors.initials: Y
authors.lastname: Fukunaka
authors.forename: R
authors.initials: R
authors.lastname: Hwang
authors.forename: V
authors.initials: V
authors.lastname: De Luca
authors.forename: O
authors.initials: O
authors.lastname: Ohmori
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chuang
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics* / Q000523:psychology; D004843:Epistasis, Genetic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic