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

Authors Rodrigues-Silva C, Semedo AT, Neri HFS, Vianello RP, Galaviz-Hernández C, Sosa-Macías M, de Brito RB, Ghedini PC

Received 22 August 2019

Accepted for publication 21 December 2019

Published 11 February 2020 Volume 2020:16 Pages 427—432

DOI https://doi.org/10.2147/NDT.S228103

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder


Christielly Rodrigues-Silva,1 Agostinho Tavares Semedo,1 Hiasmin Franciely da Silva Neri,1 Rosana Pereira Vianello,2 Carlos Galaviz-Hernández,3 Martha Sosa-Macías,3 Rodrigo Bernini de Brito,1,4 Paulo César Ghedini1

1Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil; 2Empresa Brasileira de Pesquisa Agropecuária - Embrapa, Santo Antônio de Goiás, GO, Brazil; 3Instituto Politécnico Nacional, Academia de Genómica, CIIDIR-Durango, Durango, México; 4Brain Institute Medical Clinic, Bueno Medical Center Building, Goiânia, GO, Brazil

Correspondence: Paulo César Ghedini
Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biológicas, UFG, Cep 74690-900, Goiânia, GO, Brazil
Tel +55 62 3521-1725
Email pcghedini@gmail.com

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.

Keywords: schizophrenia, CYP2C19*2, CYP2C19*17, treatment response, clozapine

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