Pharmacogenomic Associations With Weight Gain in Olanzapine Treatment of Patients Without Schizophrenia
| Autor: | Fangyi Zhao, John P. Houston, Vicki L. Ellingrod, Jared Kohler, Robert R. Conley, Jeffrey R. Bishop, Katherine M. Ostbye, Vicki Poole Hoffmann, Bonnie Fijal |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Oncology Olanzapine medicine.medical_specialty Bipolar Disorder medicine.medical_treatment Population Single-nucleotide polymorphism Weight Gain Polymorphism Single Nucleotide Linkage Disequilibrium Benzodiazepines Depressive Disorder Treatment-Resistant Borderline Personality Disorder Internal medicine medicine Humans Psychiatry education Antipsychotic Alleles Genetic Association Studies ANKK1 education.field_of_study business.industry Mental Disorders Weight change Middle Aged Risperidone medicine.disease Psychiatry and Mental health Pharmacogenetics Schizophrenia Female medicine.symptom business Weight gain Antipsychotic Agents medicine.drug |
| Zdroj: | The Journal of Clinical Psychiatry. 73:1077-1086 |
| ISSN: | 0160-6689 |
| Popis: | 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. METHOD 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. |
| Databáze: | OpenAIRE |
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