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The CYP2C19*2 and CYP2C19*17 Polymorphisms Influence Responses to Clozapine for the Treatment of Schizophrenia.


ABSTRACT: Introduction:Clozapine (CLZ) is the gold standard drug for treatment-refractory schizophrenia (TRS). However, approximately 30% of patients partially respond to CLZ, defining this subset with super refractory schizophrenia (SRS). Alterations in enzyme activity may affect CLZ responses; the CYP3A4, CYP1A2 and CYP2C19 genes are primarily responsible for CLZ metabolism. Objective:The aim of this study was to assess if CYP2C19 variants were associated with TRS or SRS. Methods:CYP2C19*2 loss-of-function and CYP2C19*17 gain-of-function polymorphism genotype testing were performed in 108 individuals undergoing pharmacological treatment for TRS or SRS. DNA was extracted and polymorphisms were analyzed by polymerase chain reaction (PCR) and sequencing. Results:CYP2C19*17 had positive correlations with SRS and lower Brief Psychiatric Rating Scale (BPRS) scores for TRS. In addition, CYP2C19*2 was associated with lower CLZ dosages for TRS. Conclusion:These results show that CYP2C19*2 and CYP2C19*17 polymorphisms influence CLZ responses during schizophrenia treatment.

SUBMITTER: Rodrigues-Silva C 

PROVIDER: S-EPMC7023876 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The CYP2C19*2 and CYP2C19*17 Polymorphisms Influence Responses to Clozapine for the Treatment of Schizophrenia.

Rodrigues-Silva Christielly C   Semedo Agostinho Tavares AT   Neri Hiasmin Franciely da Silva HFDS   Vianello Rosana Pereira RP   Galaviz-Hernández Carlos C   Sosa-Macías Martha M   de Brito Rodrigo Bernini RB   Ghedini Paulo César PC  

Neuropsychiatric disease and treatment 20200211


<h4>Introduction</h4>Clozapine (CLZ) is the gold standard drug for treatment-refractory schizophrenia (TRS). However, approximately 30% of patients partially respond to CLZ, defining this subset with super refractory schizophrenia (SRS). Alterations in enzyme activity may affect CLZ responses; the CYP3A4, CYP1A2 and CYP2C19 genes are primarily responsible for CLZ metabolism.<h4>Objective</h4>The aim of this study was to assess if CYP2C19 variants were associated with TRS or SRS.<h4>Methods</h4>C  ...[more]

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