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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, BrazilCorrespondence: Paulo César GhediniLaboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biológicas, UFG, Cep 74690-900, Goiânia, GO, BrazilTel +55 62 3521-1725Email pcghedini@gmail.comIntroduction: 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 |
