title: Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia.
abstract: OBJECTIVE
  Pharmacogenomic analyses of weight gain during treatment with second-generation antipsychotics have resulted in a number of associations with variants in ankyrin repeat and kinase domain containing 1 (ANKK1)/dopamine D2 receptor (DRD2) and serotonin 2C receptor (HTR2C) genes. These studies primarily assessed subjects with schizophrenia who had prior antipsychotic exposure that may have influenced the amount of weight gained from subsequent therapies. We assessed the relationships between single-nucleotide polymorphisms (SNPs) in these genes with weight gain during treatment with olanzapine in a predominantly antipsychotic-naive population.
  
  
  METHODS
  The association between 5 ANKK1, 54 DRD2, and 11 HTR2C SNPs and weight change during 8 weeks of olanzapine treatment was assessed in 4 pooled studies of 205 white patients with diagnoses other than schizophrenia who were generally likely to have had limited previous antipsychotic exposure.
  
  
  RESULTS
  The A allele of DRD2 rs2440390(A/G) was associated with greater weight gain in the entire study sample (P = .0473). Three HTR2C SNPs in strong linkage disequilibrium, rs6318, rs2497538, and rs1414334, were associated with greater weight gain in women but not in men (P = .0032, .0012, and .0031, respectively). A significant association with weight gain for 2 HTR2C SNPs previously reported associated with weight gain, -759C/T (rs3813929) and -697G/C (rs518147), was not found.
  
  
  CONCLUSIONS
  Associations between weight gain and HTR2C and DRD2 variants in whites newly exposed to olanzapine may present opportunities for the individualization of medication selection and development based on differences in adverse events observed across genotype groups.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA. johnphilliphouston@gmail.com
authors.forename: John P
authors.initials: JP
authors.lastname: Houston
authors.forename: Jared
authors.initials: J
authors.lastname: Kohler
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Ostbye
authors.forename: Fangyi
authors.initials: F
authors.lastname: Zhao
authors.forename: Robert R
authors.initials: RR
authors.lastname: Conley
authors.forename: Vicki
authors.initials: V
authors.lastname: Poole Hoffmann
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Fijal
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics; D001883:Borderline Personality Disorder / Q000188:drug therapy / Q000235:genetics; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D000077152:Olanzapine; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine