Methotrexate pharmacogenetics in Uruguayan adults with hematological malignant diseases
Author
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Giletti, Andrea
Author
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Vitala, Marcelo
Author
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Lorenzo, Mariana
Author
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Cardozo, Patricia
Author
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Borelli, Gabriel
Author
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Gabus, Raúl
Author
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Martínez, Lem
Author
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Díaz, Lilian
Author
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Assar Cuevas, Rodrigo
Author
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Rodriguez, María Noel
Admission date
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2018-06-08T20:20:05Z
Available date
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2018-06-08T20:20:05Z
Publication date
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2017
Cita de ítem
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European Journal of Pharmaceutical Sciences 109 (2017) 480–485
es_ES
Identifier
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http://dx.doi.org/10.1016/j.ejps.2017.09.006
Identifier
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https://repositorio.uchile.cl/handle/2250/148743
Abstract
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Background: Individual variability is among the causes of toxicity and interruption of treatment in acute lymphoblastic
leukemia (ALL) and severe non-Hodgkin lymphoma (NHL) patients under protocols including
Methotrexate (MTX): 2,4-diamino-N10-methyl propyl-glutamic acid.
Methods: 41 Uruguayan patients were recruited. Gene polymorphisms involved in MTX pathway were analyzed
and their association with treatment toxicities and outcome was evaluated.
Results: Genotype distribution and allele frequency were determined for SLC19A1 G80A, MTHFR C677T and
A1298C, TYMS 28 bp copy number variation, SLCO1B1 T521C, DHFR C−1610G/T, DHFR C-680A, DHFR A-317G and
DHFR 19 bp indel. Multivariate analysis showed that DHFR-1610G/T (OR =0.107, p=0.018) and MTHFR677T
alleles (OR= 0.12, p=0.026) had a strong protective effect against hematologic toxicity, while DHFR-1610CC
genotype increased this toxicity (OR =9, p=0.045). No more associations were found.
Conclusions: The associations found between gene polymorphisms and toxicities in this small cohort are encouraging
for a more extensive research to gain a better dose individualization in adult ALL and NHL patients.
Besides, genotype distribution showed to be different from other populations, reinforcing the idea that genotype
data from other populations should not be extrapolated to ours.
es_ES
Patrocinador
dc.description.sponsorship
Comisión Sectorial de Investigación
Científica (grant number CSIC I+D 808), Agencia Nacional de
Investigación e Innovación (grant number ANII
POS_NAC_2014_1_102979) and Fundación Manuel Pérez, Uruguay.