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Research Article

Pharmacoepigenetics in Childhood Acute Lymphoblastic leukemia: Involvement of miRNA Polymorphisms in Hepatotoxicity

, , , , , , , & show all
Pages 409-417 | Received 16 Oct 2017, Accepted 18 Dec 2017, Published online: 23 Mar 2018
 

Abstract

Aim: Hepatotoxicity is one of the most common drug-related toxicities during the treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA function could be modulated by SNPs. As a consequence, we hypothesized that variants in miRNAs could be associated with drug-induced hepatotoxicity. Methods: We analyzed 213 SNPs in 206 miRNAs in a cohort of 179 children with ALL homogeneously treated. Results: rs2648841 in miR-1208 was the most significant SNP during consolidation phase after false discovery rate correction, probably through an effect on its target genes DHFR, MTR and MTHFR. Conclusion: These results point out the possible involvement of SNPs in miRNAs in toxicity to chemotherapy in children with ALL.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/epi-2017-0138

Financial & competing interests disclosure

This study was funded by the Basque Government (IT989-16). Support by the Spanish National Genotyping Center (CeGen) is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was funded by the Basque Government (IT989-16). Support by the Spanish National Genotyping Center (CeGen) is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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