Importância dos polimorfismos C3435T e C1236T do gene de resistência a múltiplas drogas (MDR1) na resposta ao tratamento com mesilato de imatinib em pacientes com Leucemia Mielóide Crônica (LMC)

• Autor(a) principal: Pereira, Lucas Carlos Gomes
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/00130000027hj
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/3100
• topic: LMC; MDR1; Polimorfismo genético; PCR-RFLP; LMC; MDR1; Genetic polymorphism; PCR-RFLP; CIENCIAS DA SAUDE::FARMACIA

In recent years, the evolution of health expenditures and specifically drugs, has worried governments. Among the various specialties, oncology is among those dealing with the greatest difficulties in the management of drug therapy. It is known that patients treated with various drugs have variability of response and susceptibility to drug toxicity. In present work, we study the role of Multiple Drug Resistance gene (MDR1) polymorphisms C1236T and C3435T frequencies and response to treatment with imatinib mesylate in 96 patients with chronic myeloid leukemia (CML). A total of 96 patients with CML were treated according to the Brazilian National Cancer Institute (INCA) guidelines and the blood samples were collected for genotyping. Genomic DNA was extracted and C1236T and C3435T polymorphisms genotyping was performed by the polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP), which detects a variation in length of a DNA fragment generated (370pb and 340pb) by a specific endonuclease in a specific site of the genome (HaeIII and MboI). Of the 96 CML samples, 31 samples were homozygous (CC), 13 homozygous (TT) and 52 heterozygous (CT) for exon 12 (1236). For the exon 26 (3435), 35 were homozygous (CC), 12 homozygous (TT) and 49 heterozygotes (CT). All frequencies for both polymorphisms were in Hardy-Weinberg equilibrium (p = 0.229 and q = 0.414). We found percentage association between polymorphisms and their distribution in different populations, and the response to treatment both cytogenetic and molecular difference was not statistically significant (p <0.05) when compared to age and sex presented response by patients and also no statistical difference (p <0,050). We conclude that the observed allele frequency for exons 1236 were 59.4% for C and 40.6% for T and the frequencies for the exon 3435 were 62.0% for C and 38.0% for T. That the relationship between the frequencies of polymorphisms of MDR1 in populations of different geographic locations, can provide tools that help in choosing a more appropriate and effective treatment of CML.