Pharmacogenetics of clozapine response and induced weight gain: A comprehensive review and meta-analysis
Autor: | Raffaella Calati, Florence Gressier, Stefano Porcelli, Alessandro Serretti |
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Přispěvatelé: | Gressier, F, Porcelli, S, Calati, R, Serretti, A, Gressier, Florence, Porcelli, STEFANO LUIGI, Calati, Raffaella, Serretti, Alessandro |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
rs6311
Databases Factual Rs6313 medicine.drug_class medicine.medical_treatment Atypical antipsychotic Single-nucleotide polymorphism Bioinformatics 03 medical and health sciences 0302 clinical medicine Humans Medicine Pharmacology (medical) Clozapine efficacy Antipsychotic Clozapine Biological Psychiatry Weight gain Genetics Pharmacology Pharmacodynamic business.industry Mental Disorders Pharmacogenetic Serotonergic gene 030227 psychiatry Antipsychotic Agent Neurology Pharmacogenetics Psychiatry and Mental Health Meta-analysis Mental Disorder Neurology (clinical) business 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug Human |
Popis: | Clozapine (CLZ) is the prototype atypical antipsychotic and it has many advantages over other antipsychotic drugs. Several data suggest that both CLZ response and induced weight gain are strongly determined by genetic variability. However, results remain mainly inconclusive. We aim to review the literature data about pharmacogenetics studies on CLZ efficacy, focusing on pharmacodynamic genes. Further, we performed meta-analyses on response when at least three studies for each polymorphism were available. Sensitivity analyses were conducted on Caucasian population when feasible. Electronic literature search was performed to identify pertinent studies published until May 2014 using PubMed, ISI Web of Knowledge and PsycINFO databases. For meta-analyses, data were entered and analyzed through RevMan version 5.2 using a random-effect model. Our literature search yielded 9266 articles on CLZ; among these, we identified 59 pertinent pharmacogenetic studies. Genotype data were retrieved for 14 polymorphisms in 9 genes. Among these, we had available data from at least three independent samples for 8 SNPs in 6 genes to perform meta-analyses: DRD2 rs1799732, DRD3 rs6280, HTR2A rs6313, rs6311, rs6314, HTR2C rs6318, HTR3A rs1062613, TNFa rs1800629. Although literature review provided conflicting results, in meta-analyses three genetic variants within serotonin genes resulted associated to CLZ response: rs6313 and rs6314 within HTR2A gene and rs1062613 within HT3A gene. On the other hand, no clear finding emerged for CLZ-induced weight gain. Our results suggest a possible serotonergic modulation of CLZ clinical response. (C) 2015 Elsevier B.V. and ECNP. All rights reserved. Clozapine (CLZ) is the prototype atypical antipsychotic and it has many advantages over other antipsychotic drugs. Several data suggest that both CLZ response and induced weight gain are strongly determined by genetic variability. However, results remain mainly inconclusive. We aim to review the literature data about pharmacogenetics studies on CLZ efficacy, focusing on pharmacodynamic genes. Further, we performed meta-analyses on response when at least three studies for each polymorphism were available. Sensitivity analyses were conducted on Caucasian population when feasible. Electronic literature search was performed to identify pertinent studies published until May 2014 using PubMed, ISI Web of Knowledge and PsycINFO databases. For meta-analyses, data were entered and analyzed through RevMan version 5.2 using a random-effect model. Our literature search yielded 9266 articles on CLZ; among these, we identified 59 pertinent pharmacogenetic studies. Genotype data were retrieved for 14 polymorphisms in 9 genes. Among these, we had available data from at least three independent samples for 8 SNPs in 6 genes to perform meta-analyses: DRD2 rs1799732, DRD3 rs6280, HTR2A rs6313, rs6311, rs6314, HTR2C rs6318, HTR3A rs1062613, TNFa rs1800629. Although literature review provided conflicting results, in meta-analyses three genetic variants within serotonin genes resulted associated to CLZ response: rs6313 and rs6314 within HTR2A gene and rs1062613 within HT3A gene. On the other hand, no clear finding emerged for CLZ-induced weight gain. Our results suggest a possible serotonergic modulation of CLZ clinical response. |
Databáze: | OpenAIRE |
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