title: Association of polyaminergic loci with anxiety, mood disorders, and attempted suicide.
abstract: BACKGROUND
  The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression.
  
  
  RESULTS
  We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes.
  
  
  CONCLUSIONS
  These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate and distinct risk alleles. As several of these polymorphisms are associated with gene expression, these findings may provide mechanisms to explain the alterations in polyamine metabolism which have been observed in psychiatric disorders.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Fiori
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wanner
authors.forename: Valérie
authors.initials: V
authors.lastname: Jomphe
authors.forename: Jordie
authors.initials: J
authors.lastname: Croteau
authors.forename: Frank
authors.initials: F
authors.lastname: Vitaro
authors.forename: Richard E
authors.initials: RE
authors.lastname: Tremblay
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bureau
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D001008:Anxiety Disorders / Q000235:genetics* / Q000523:psychology; D002170:Canada; D005602:France / Q000208:ethnology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D019964:Mood Disorders / Q000235:genetics* / Q000523:psychology; D015999:Multivariate Analysis; D016017:Odds Ratio; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011073:Polyamines / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D013097:Spermine Synthase / Q000235:genetics; D013406:Suicide, Attempted; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D009953:Ornithine-Oxo-Acid Transaminase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D013097:Spermine Synthase; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase