title: Dopamine receptor D3 genotype association with greater acute positive symptom remission with olanzapine therapy in predominately caucasian patients with chronic schizophrenia or schizoaffective disorder.
abstract: OBJECTIVE
  To test association of dopamine receptor D3 (DRD-3) gene polymorphisms with olanzapine response in genetic samples from a registration phase clinical trial.
  
  
  METHODS
  Eighty-eight acutely ill patients with schizophrenia or schizoaffective disorder were genotyped for ser-9-gly (rs6280) and 23 other polymorphisms within the DRD-3 gene. Allelic association of clinical response (mean baseline- to-endpoint reduction in Positive and Negative Syndrome Scale [PANSS] total and subscores) over 6 weeks of olanzapine treatment was assessed using repeated measures analysis of variance.
  
  
  RESULTS
  Ser-9-gly genotypes were associated with differences in PANSS total score improvement from baseline to 6 weeks (p = 0.021). This association was most notable for improvement in positive symptoms (p = 0.0001), with patients with gly/gly genotype significantly more responsive. More patients with the gly/gly genotype had greater positive symptom remission (endpoint rating of minimal or none on all PANSS positive items, 39.1%) compared with patients with gly/ser and ser/ser genotypes (13.8%; p = 0.033). DRD-3 polymorphisms in disequilibrium with ser-9-gly were also significantly associated with greater positive symptom improvement (p = 0.0009-0.021), and one not in complete linkage disequilibrium, with lesser improvement (p = 0.027).
  
  
  CONCLUSIONS
  Gly/gly DRD-3 genotype predicted statistically and clinically significantly better acute positive symptom reduction compared with other ser-9-gly genotypes in patients treated with olanzapine.
authors.affiliation: Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. adamsda@lilly.com
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.forename: Sandra
authors.initials: S
authors.lastname: Close
authors.forename: Mark
authors.initials: M
authors.lastname: Farmen
authors.forename: Anncatherine M
authors.initials: AM
authors.lastname: Downing
authors.forename: Alan
authors.initials: A
authors.lastname: Breier
authors.forename: John P
authors.initials: JP
authors.lastname: Houston
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome; D044465:White People
chemical_list: D014150:Antipsychotic Agents; D050637:Receptors, Dopamine D3; D001569:Benzodiazepines; D000077152:Olanzapine