Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia
Data(s) |
02/02/2016
02/02/2016
10/03/2014
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Resumo |
Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL. |
Identificador |
PLOS ONE 9(3) 2014 : (2014) // Article ID e91261 1932-6203 http://hdl.handle.net/10810/17175 10.1371/journal.pone.0091261 |
Idioma(s) |
eng |
Publicador |
Public Library Science |
Relação |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091261#abstract0 |
Direitos |
2014 López-López et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited info:eu-repo/semantics/openAccess |
Palavras-Chave | #molecular epidemiology #linking polimorphisms #polimirts database #drug-resistance #complex-traits #target sites #cancer #methotrexate #childhood #toxicity |
Tipo |
info:eu-repo/semantics/article |