Clozapine toxicity in treatment of patients with schizophrenia: possible relation to genetic polymorphisms

• Grant number: 19/19460-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2019
• Effective date (End): March 31, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: João Kleber Novais Pereira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Schizophrenia is a serious mental illness characterized by positive, negative and cognitive symptoms that affect almost every aspect of mental activity, including perception, attention, memory and emotion affecting approximately 1% of the global population. Its treatment depends on several clinical parameters, being antipsychotics the main therapeutic class of choice for its treatment. Although this therapeutic class is extremely effective, some patients remain refractory to treatment, determining a Treatment-Resistant Schizophrenia (TRS) group. Clozapine (CLZ) is a second generation antipsychotic indicated for TRS. Despite its effectiveness, CLZ is related to serious adverse reactions such as agranulocytosis that can be fatal if left untreated, as well as long-term reactions such as weight gain induction and metabolic changes that may result in future heart disease. This study aims to study the correlation of genetic polymorphisms of cytochrome P450, ABC membrane transporters and HLA system, as well as obesity-related genes LEP, LEPR and MC4R in patients with schizophrenia treated with CLZ. For this, we will use blood sample for extraction of genomic DNA. The genetic profiles of the cited genes will be performed by q-PCR and will correlate with possible adverse reactions. Statistical analysis will be performed using chi-square, Fisher's exact, Mann-Whitney and Anova tests. That is, this study aims to verify the genetic influences on CLZ response. So we hope to provide tools that help doctors make better decisions for each patient by providing accurate, personalized and more humanized medicine. (AU)