Análise da influência dos polimorfismos 1236C>T, 2677G>T/A E 3435C>T do gene ABCB1 na resposta ao tratamento com clozapina

• Autor(a) principal: Salamanca, Ayda Luz Malaver
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/001300000ckkm
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/5291
• topic: Farmacogenética; ABCB1; Polimorfismos; Clozapina; Refratário; Super refratário; Pharmacogenetics; Polymorphisms; Clozapine; Refractory; Superrefractory; CIENCIAS BIOLOGICAS

Clozapine (CLZ) is the antipsychotic drug of choice in treatment refractory schizophrenia (TRS), however 30% of the patients with TRS don’t have full response to treatment with CLZ, these patients are considered to have super refractory schizophrenia (SRS). The response variability to treatment with CLZ may be associated with alterations of the CLZ plasma levels promoted by 1236C>T, 2677G>T/A e 3435C>T ABCB1 gene polymorphisms. ABCB1 is a transmembrane glycoprotein of transport, which export drugs from the intracellular to the extracellular space. ABCB1 polymorphisms cause structurally and functional protein changes that influence the intracellular CLZ levels and, consequently, promoting therapy failure. This work had the aim to establish the relation between the 1236C>T, 2677G>T/A e 3435C>T ABCB1 polymorphisms and the CLZ treatment response. This study included a total of 68 patients, 34 of whom were classified as TRS (CLZ responders) and 34 as SRS (CLZ non-responders). All patients were in use of CLZ for at least one year. For the genotype test was extracted genomic DNA, following for PCR and sequencing techniques. It was not observed any differences in allelic and genotype distribution between 1236C>T, 2677G>T/A and 3435C>T polymorphisms between RS and SRS groups. The polymorphisms not influenced the CLZ dose level, and percentage of BPRS change. In the same way, the results not showed relation between age, coffee intake, smoking behaviors and ethnicity and the CLZ treatment response, however, was evidenced a higher proportion of female patients in the SRS group when compared with the TRS group. In opposite, a lower proportion of male patients was observed in the SRS than the TRS group. Taken together, the results here obtained showed no association between 12361236C>T, 2677G>T/A e 3435C>T polymorphisms of ABCB1 gene and failure to CLZ treatment.