Análise da influência dos polimorfismos 1236C>T, 2677G>T/A E 3435C>T do gene ABCB1 na resposta ao tratamento com clozapina
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2015-12-04
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Universidade Federal de Goiás
Resumo
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.
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SALAMANCA, A. L. M. Análise da influência dos polimorfismos 1236C>T, 2677G>T/A E 3435C>T do gene ABCB1 na resposta ao tratamento com clozapina. 2015. 62 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2015.