title: Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women.
abstract: BACKGROUND
  Tobacco smoking is the leading preventable cause of death in the developed world. Identifying risk factors for smoking may lead to more effective treatments. Genome wide association studies revealed a relationship between development of nicotine dependence and a single-nucleotide polymorphism (SNP, rs16969968) of the nicotine acetylcholine receptor (nAChR) alpha-5 subunit gene (CHRNA5). The relationship between this SNP and other factors contributing to smoking behavior such as smoking cue reactivity is unclear.
  
  
  METHODS
  We assessed the role of rs16969968 on brain functional MRI (fMRI) reactivity to smoking cues by studying nicotine dependent women with the nicotine dependence 'risk' allele (A allele, N=14) and without the 'risk' allele (G/G smokers, N=10). Nicotine dependence severity, as assessed with the Fagerstrom test for nicotine dependence, smoking pack-years, and expired carbon monoxide levels, were equivalent in these groups.
  
  
  RESULTS
  We observed a group difference in fMRI reactivity; women without the A allele (G/G smokers) showed greater fMRI reactivity to smoking images in brain areas related to memory and habitual behavior such as the hippocampus and dorsal striatum.
  
  
  CONCLUSIONS
  Our finding suggests that nicotine-dependent smokers lacking the rs16969968 A allele are more likely to recall smoking-related memories and engage in habitual responding to smoking cues than A allele smokers. Although more studies are necessary to determine the mechanism underlying and significance of this cue reactivity difference, these data suggest that smokers may develop and remain nicotine dependent due to different factors including genetics and cue reactivity. This finding may have implications for personalizing smoking treatment.
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA. ajanes@mclean.harvard.edu
authors.forename: Amy C
authors.initials: AC
authors.lastname: Janes
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Sean P
authors.initials: SP
authors.lastname: David
authors.forename: Blaise Deb
authors.initials: BD
authors.lastname: Frederick
authors.forename: Stephen
authors.initials: S
authors.lastname: Haddad
authors.forename: Aditi
authors.initials: A
authors.lastname: Basu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: A Eden
authors.initials: AE
authors.lastname: Evins
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Kaufman
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology*; D003463:Cues; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic