title: Weight gain associated with the -759C/T polymorphism of the 5HT2C receptor and olanzapine.
abstract: BACKGROUND
  Weight gain from atypical antipsychotic use has become a significant problem. Recent reports have liked the -759 polymorphism of the 5HT2C receptor and obesity as well as weight gain from chlorpromazine, risperidone, and clozapine.
  
  
  OBJECTIVE
  To determine associations between weight gain during olanzapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene.
  
  
  METHODS
  This study included 42 acutely ill patients with schizophrenia (DSM-IV). Weekly assessments included Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a fixed dose (7.5-20 mg/day) for 2-6 weeks. A 24 hr plasma level was obtained at the endpoint visit. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor.
  
  
  RESULTS
  A chi-square analysis was conducted comparing the distribution of T and C alleles in subjects grouped as gaining more or less than 5, 7, and 10% of their baseline weight during treatment with olanzapine. A threshold of 10% was found to be significant. The distribution of T alleles was higher in subjects not gaining 10% of more of their body weight compared who did gain significant weight (11/27 (40.7%) vs. 0/15 (100%), chi2 = 11.805, P = 0.0035).
  
  
  CONCLUSIONS
  Subjects with a T allele of the 5HT2C receptor -759C/T polymorphism may have a lower incidence of weight gain from olanzapine over a 6 week period compared to those with the C allele. These results need to be replicated.
authors.affiliation: University of Iowa, College of Pharmacy, Iowa, USA. vicki-ellingrod@uiowa.edu
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Perry
authors.forename: John C
authors.initials: JC
authors.lastname: Ringold
authors.forename: Brian C
authors.initials: BC
authors.lastname: Lund
authors.forename: Kristy
authors.initials: K
authors.lastname: Bever-Stille
authors.forename: Frank
authors.initials: F
authors.lastname: Fleming
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Holman
authors.forename: Del
authors.initials: D
authors.lastname: Miller
mesh_terms: D000483:Alleles; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000097:blood / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D001569:Benzodiazepines; D000077152:Olanzapine