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Previous issue date: 2013-05-02 / 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. / Neste estudo, o papel dos polimorfismos C1236T e C3435T do gene de
Resistência a Múltiplas Drogas (MDR1) foram investigados em relação à
frequência e a resposta ao tratamento com imatinibe em pacientes com
leucemia mielóide crônica (LMC). Um total de 96 pacientes com LMC foram
tratados de acordo com as diretrizes do Instituto Nacional do Câncer (INCA) e
amostras de sangue foram coletadas para genotipagem do gene MDR
(Resistência à Multiplas Drogas). O DNA genômico foi extraído e a
genotipagem dos polimorfismos C1236T e C3435T foi realizada por meio da
reação em cadeia da polimerase com fragmentos de restrição (PCR-RFLP),
que detectou uma variação no comprimento de um fragmento de DNA gerado
(370pb e 340pb) por uma endonuclease específica em um sítio específico
do genoma (HaeIII e Mbol). Analisando as 96 amostras de pacientes para o
polimorfismo no éxon 12 (1236) com LMC, 31 amostras apresentaram
homozigose (CC), 13 homozigose (TT) e 52 heterozigose (CT). Para o estudo
do polimorfismo no éxon 26 (3435), 35 foram homozigotas (CC), 12
homozigotas (TT) e 49 heterozigotas (CT). Todas as frequências para ambos
os polimorfismos apresentaram-se em equilíbrio de Hardy-Weinberg (p = 0,229
e q = 0,414). Foi encontrada associação do percentual dos polimorfismos
estudados em relação à distribuição dos mesmos em grupos de diferentes
localizações geográficas, e sobre a resposta ao tratamento tanto citogenética e
molecular, não houve diferença estatísticamente significante (p<0,05), quando
foi comparado à idade e ao gênero apresentados pelos pacientes e a resposta
também não houve diferença estatística (p<0,05). Conclui-se que as
frequências alélicas observadas para o éxon 1236 foram de 59,4% para C e
40,6% para T e as frequências para o éxon 3435 foram de 62,0% para C e
38,0% para T e que a relação entre as frequências de polimorfismos de MDR1
nas populações de diferentes localizações geográficas, pode fornecer
ferramentas que auxiliem na escolha de um tratamento mais adequado e eficaz
da LMC.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tede/3100 |
| Date | 02 May 2013 |
| Creators | Pereira, Lucas Carlos Gomes |
| Contributors | Lacerda, Elisangela de Paula Silveira, Vilanova-Costa, Cesar Augusto Sam Tiago |
| Publisher | Universidade Federal de Goiás, Programa de Pós-graduação em Ciências Farmacêuticas (FF), UFG, Brasil, Faculdade de Medicina - FM (RG) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG |
| Rights | http://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess |
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