TY - JOUR
T1 - The CYP2C19*2 and CYP2C19*17 polymorphisms influence responses to clozapine for the treatment of schizophrenia
AU - Rodrigues-Silva, Christielly
AU - Semedo, Agostinho Tavares
AU - Neri, Hiasmin Franciely da Silva
AU - Vianello, Rosana Pereira
AU - Galaviz-Hernández, Carlos
AU - Sosa-Macías, Martha
AU - de Brito, Rodrigo Bernini
AU - Ghedini, Paulo César
N1 - Publisher Copyright:
© 2020 Rodrigues-Silva et al.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - CYP2C1917
KW - CYP2C192
KW - Clozapine
KW - Schizophrenia
KW - Treatment response
UR - http://www.scopus.com/inward/record.url?scp=85079500986&partnerID=8YFLogxK
U2 - 10.2147/NDT.S228103
DO - 10.2147/NDT.S228103
M3 - Artículo
AN - SCOPUS:85079500986
SN - 1176-6328
VL - 16
SP - 427
EP - 432
JO - Neuropsychiatric Disease and Treatment
JF - Neuropsychiatric Disease and Treatment
ER -