Pharmacoepigenetics in childhood acute lymphoblastic leukemia: involvement of miRNA polymorphisms in hepatotoxicity

被引：11

作者：

Gutierrez-Camino, Angela ^{[1
]}

Umerez, Maitane ^{[1
]}

Santos, Borja ^{[1
]}

Martin-Guerrero, Idoia ^{[1
]}

Garcia de Andoin, Nagore ^{[2
,3
]}

Sastre, Ana ^{[4
]}

Navajas, Aurora ^{[5
,6
]}

Astigarraga, Itziar ^{[3
,5
,6
]}

Garcia-Orad, Africa ^{[1
,6
]}

机构：

[1] Univ Basque Country, UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Leioa, Spain

[2] Univ Hosp Donostia, Dept Pediat, San Sebastian, Spain

[3] Univ Basque Country, UPV EHU, Dept Pediat, Leioa, Spain

[4] Univ Hosp La Paz, Dept Oncohematol, Madrid, Spain

[5] Univ Hosp Cruces, Dept Pediat, Baracaldo, Spain

[6] BioCruces Hlth Res Inst, Baracaldo, Spain

来源：

EPIGENOMICS | 2018年 / 10卷 / 04期

关键词：

chemotherapy; childhood acute lymphoblastic leukemia; hepatotoxicity; methotrexate; miRNAs; SNPs; LIVER-INJURY; GENOME-WIDE; METHOTREXATE; TOXICITY; CHEMOTHERAPY; GENE; SURVIVAL; PHARMACOGENETICS; HOMOCYSTEINE; ASSOCIATION;

D O I：

10.2217/epi-2017-0138

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 inmiRNAs 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.

引用

页码：409 / 417

页数：9

共 35 条

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