Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia.

Autor: Delmond KA; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil.; College of Goyazes Union, Trindade, Goiás, 75380-000, Brazil., Delleon H; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil.; Uni-Anhanguera University Center of Goias, Goiânia, Goiás, 74423-115, Brazil., Goveia RM; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil., Teixeira TM; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil., Abreu DC; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil., Mello-Andrade F; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil.; Department of Chemistry, Federal Institute of Education, Science and Technology of Goiás, Goiânia, Goiás, 74055-110, Brazil., Reis AADS; Department of Biochemistry and Molecular Biology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, 74690-900, Brazil., Silva DME; Department of Genetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, 74690-900, Brazil., Barbosa ADP; Clinical Hospital, Federal University of Goiás-UFG, Goiânia, GO, 74605-020, Brazil., Tavares RS; Clinical Hospital, Federal University of Goiás-UFG, Goiânia, GO, 74605-020, Brazil., Anunciação CE; Department of Biochemistry and Molecular Biology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, 74690-900, Brazil., Silveira-Lacerda E; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiânia, Goiás, 74690-900, Brazil. elacerda@ufg.br.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2021 Mar; Vol. 48 (3), pp. 2035-2046. Date of Electronic Publication: 2021 Mar 11.
DOI: 10.1007/s11033-020-06093-z
Abstrakt: Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient's genotypes was analyzed with the patient's response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The "G allele" of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.
Databáze: MEDLINE
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