Association of the genetic polymorphisms of metabolizing enzymes, transporters, target receptors and their interactions with treatment response to olanzapine in chinese han schizophrenia patients
| Autor: | Jing Li, Jianfei Shi, Pan Yan, Shengdong Wang, Chengpeng Wang, Bing Gao, Mingfen Song, Shuqi Wang, Haihong Fang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Olanzapine Paranoid schizophrenia UGT1A4 Genotype rs6311 medicine.drug_class Atypical antipsychotic Bioinformatics 03 medical and health sciences 0302 clinical medicine Asian People Cytochrome P-450 CYP1A2 medicine Humans Receptor Biological Psychiatry Polymorphism Genetic Schizophrenia Paranoid Multifactor dimensionality reduction business.industry Membrane Transport Proteins Middle Aged medicine.disease 030227 psychiatry Psychiatry and Mental health Treatment Outcome Schizophrenia Female business 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug |
| Zdroj: | Psychiatry Research. 293:113470 |
| ISSN: | 0165-1781 |
| DOI: | 10.1016/j.psychres.2020.113470 |
| Popis: | Olanzapine is an atypical antipsychotic drug that has been increasingly used for treatment in schizophrenia. It has been observed that olanzapine responses in schizophrenia patients vary individually, but the reason has not been elucidated. In the study, we aimed to comprehensively explore the relationships between olanzapine responses and genetic polymorphisms of drug metabolizing enzymes, transporters and target receptors, and so as to interpret the reason of good and poor responses of olanzapine. A total of 241 Chinese Han paranoid schizophrenia who treated with olanzapine alone for 4 weeks were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of olanzapine. The genetic polymorphisms were detected by improved multiple ligase detection reaction (iMLDR). Multivariate logistic regression analysis suggested that the genetic polymorphisms of CYP1A2 rs762551, UGT1A4 rs2011425, ABCB1 rs1045642, DRD2 rs1799732 and rs1799978, 5-HTR2A rs6311 were significantly associated with olanzapine response. Multifactor dimensionality reduction (MDR) analysis showed that there was a negative interaction between CYP1A2 rs762551, ABCB1 rs1045642, DRD2 rs1799978, 5-HTR2A rs6311 and the interaction model was the optimal model. Our findings could partially explain the different olanzapine outcome and provided evidence for clarifying the predictive indicators of olanzapine response in further. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect