title: Protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene variants in antipsychotic-induced weight gain.
abstract: OBJECTIVE
  Antipsychotics are effective in treating schizophrenia symptoms. However, the use of clozapine and olanzapine in particular are associated with significant weight gain. Mouse and human studies suggest that the protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene may be involved in energy metabolism, and there is evidence that it is associated with clozapine's effects on triglyceride levels. We aimed at assessing PRKAR2B's role in antipsychotic-induced weight gain in schizophrenia patients.
  
  
  METHODS
  DNA samples from adult schizophrenia or schizoaffective disorder patients of mixed ancestry were genotyped, and weight gain was assessed. We analyzed 16 tag single-nucleotide polymorphisms across the PRKAR2B gene in a Caucasian subset treated either with clozapine or olanzapine (N = 99). Linear regression based on an additive model was performed with the inclusion of relevant covariates.
  
  
  RESULTS
  Normalized per cent weight change was analyzed, revealing that patients with the minor allele at rs9656135 had a mean weight increase of 4.1%, whereas patients without this allele had an increase of 3.4%. This association is not significant after correcting for multiple testing.
  
  
  CONCLUSIONS
  Because of limited power, PRKAR2B's role in antipsychotic-induced weight gain is unclear, but biological evidence suggests that PRKAR2B may be involved. Further research in larger sample sizes is warranted.
authors.affiliation: Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Gagliano
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Natalie
authors.initials: N
authors.lastname: Freeman
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Jo
authors.initials: J
authors.lastname: Knight
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; C517837:PRKAR2B protein, human; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine
keywords: PRKAR2B; antipsychotic-induced weight gain; pharmacogenetics; polymorphisms; schizophrenia