title: Genetic interactions in the adrenergic system genes: analysis of antipsychotic-induced weight gain.
abstract: Atypical antipsychotics (AP) have high affinity for many neurotransmitter receptors. Among these receptors, APs are antagonist at α-adrenergic and β-adrenergic receptors, and this pharmacological property has been postulated to be involved in the mechanism of action of these drugs with respect to both clinical response and adverse effects.
  
  
  OBJECTIVE
  We tested the hypotheses that AP-induced weight gain is associated with genetic variation in adrenergic receptors and pathway enzymes. We analyzed nine genetic polymorphisms across seven adrenergic genes (ADRA1A, ADRA2A, ADRA2C, ADRB3, DBH, MAOA and COMT).
  
  
  METHODS
  One hundred thirty-nine patients with schizophrenia were prospectively assessed for AP-induced weight gain. The HelixTree software (Golden Helix, Bozeman, MT, USA) was employed to detect differences in genotypic distribution between weight gainer and non-weight gainer groups. Furthermore, for the dopamine β-hydroxylase haplotype, we were able to obtain both the molecular and the statistical phases, analyzing the phenotype considering both phases.
  
  
  RESULTS
  Weight gain was not associated with any adrenergic gene.
  
  
  CONCLUSIONS
  Our results suggest that genetic polymorphisms in the adrenergic system may not play a major role in AP-induced weight gain; however, adrenergic 2A receptor gene that produced previously the most consistent associations with this phenotype showed a significant interaction with the monoamine oxidase A in weight gainers.
authors.affiliation: Neurogenetics Section, Centre for Addictions and Mental Health, Toronto, ON, Canada. vincenzo_deluca@camh.net
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Renan P
authors.initials: RP
authors.lastname: Souza
authors.forename: Emanuela
authors.initials: E
authors.lastname: Viggiano
authors.forename: Laertes
authors.initials: L
authors.lastname: Sickert
authors.forename: Celine
authors.initials: C
authors.lastname: Teo
authors.forename: Clement
authors.initials: C
authors.lastname: Zai
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011941:Receptors, Adrenergic / Q000235:genetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
chemical_list: C547768:ADRA2A protein, human; D014150:Antipsychotic Agents; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase