title: Why do young women smoke? VII COMT as a risk modifying gene for Nicotine dependence - role of gene-gene interaction, personality, and environmental factors.
abstract: OBJECTIVE
  Catechol-O-methyltransferase (COMT) may be a risk modifying gene for Nicotine dependence (ND) rather than a direct susceptibility gene for this phenotype. Brain nicotinic cholinergic receptors modulate dopaminergic transmission, and several variants within the neighboring CHRNA5-CHRNA3 genes have been associated with ND. Therefore, it is biologically reasonable to study the interactive contribution of COMT and the CHRNA5 and CHRNA3 genes to ND.
  
  
  METHODS
  Using a case-control sample of 90 young, Israeli, Jewish female smokers (FTND ≥ 4) and 108 controls (FTND = 0 during heaviest period of smoking), we studied association with ND of 8 COMT tagging SNPs, their interaction with tagging CHRNA5-A3 SNPs and the role of background, personality, and environmental factors.
  
  
  RESULTS
  None of the COMT SNPs were associated directly with ND. In pairwise interaction analysis of SNPs from the two loci (COMT SNP-CHRNA5-CHRNA3 SNP), the interaction of intronic COMT SNP, rs9332377, with CHRNA3 3'UTR SNP rs660652 was significantly associated with ND (p = 0.0005), withstanding correction for multiple testing.
  
  
  CONCLUSIONS
  Addition of the genetic interaction variable into a model of non-genetic ND predictors [parental smoking, novelty seeking (NS), and lifetime history of trauma], substantially increases the percentage of ND variance explained by the model, as well as the percentage of cases correctly identified by it.
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Greenbaum
authors.forename: Kyra Sarner
authors.initials: KS
authors.lastname: Kanyas
authors.forename: Amihai
authors.initials: A
authors.lastname: Rigbi
authors.forename: Anna
authors.initials: A
authors.lastname: Alkelai
authors.forename: Yoav
authors.initials: Y
authors.lastname: Kohn
authors.forename: Bernard
authors.initials: B
authors.lastname: Lerer
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D010551:Personality; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012931:Social Environment; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000378:metabolism / Q000523:psychology*; D044465:White People; D014930:Women; D055815:Young Adult
chemical_list: D002394:Catechol O-Methyltransferase; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human