title: Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia.
abstract: Clinical trial data were evaluated for the association between 22 single-nucleotide polymorphisms (SNPs) and response in acutely ill patients diagnosed with schizophrenia, schizoaffective disorder or schizophreniform disorder, who were treated with oral risperidone. All patients in the exploratory (78 African Americans) and validation (65 whites) data sets received risperidone 2-6 mg per day over 2-12 weeks. Two SNPs were found to have significant associations with response to risperidone over 2-12 weeks in both African-American and white patients and had a consistent direction of effect in both cohorts. Metabotropic glutamate receptor (GRM3) SNP, rs724226, was associated with a change in the positive and negative syndrome scale (PANSS) total response. Catechol-O-methyltransferase (COMT) SNP, rs165599, was moderately associated with a change in the PANSS Negative score. The greater prevalence of poor-responder GRM3 and COMT alleles in white versus African-American patients might have a clinical significance in evaluating the ethnic-specific response to risperidone.
authors.affiliation: Lilly USA, LLC, Indianapolis, IN 46285, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Fijal
authors.forename: B J
authors.initials: BJ
authors.lastname: Kinon
authors.forename: S
authors.initials: S
authors.lastname: Kapur
authors.forename: V L
authors.initials: VL
authors.lastname: Stauffer
authors.forename: R R
authors.initials: RR
authors.lastname: Conley
authors.forename: H H
authors.initials: HH
authors.lastname: Jamal
authors.forename: J M
authors.initials: JM
authors.lastname: Kane
authors.forename: M M
authors.initials: MM
authors.lastname: Witte
authors.forename: J P
authors.initials: JP
authors.lastname: Houston
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D002394:Catechol O-Methyltransferase; D018967:Risperidone