Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

• Published in: The pharmacogenomics journal Vol. 9; no. 5; pp. 311 - 318
• Main Authors: Fijal, B A, Kinon, B J, Kapur, S, Stauffer, V L, Conley, R R, Jamal, H H, Kane, J M, Witte, M M, Houston, J P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2009; Nature Publishing Group
• Subjects: Administration, Oral; Adult; African Americans; African Americans - genetics; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - therapeutic use; Antipsychotics; Association analysis; Biomedical and Life Sciences; Biomedicine; Care and treatment; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - genetics; Demographic aspects; Dosage and administration; Double-Blind Method; European Continental Ancestry Group - genetics; Female; Gene Expression; Genetic aspects; Genetic Association Studies; Glutamic acid receptors (metabotropic); Human Genetics; Humans; Male; Mental disorders; Methyltransferase; Middle Aged; Oncology; original-article; Patients; Pharmacogenetics; Pharmacotherapy; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Psychopharmacology; Receptors, Metabotropic Glutamate - genetics; Risperidone; Risperidone - administration & dosage; Risperidone - therapeutic use; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - ethnology; Schizophrenia - genetics; Schizophrenic Psychology; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Time Factors; Treatment Outcome; United States; pharmacogenomics; schizophrenia; SNP; atypical antipsychotic; single nucleotide polymorphism; risperidone
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2009.24

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.