儿童急性淋巴细胞白血病的药物基因组表观遗传学：miRNA 多态性与肝毒性的关系。
Pharmacoepigenetics in childhood acute lymphoblastic leukemia: involvement of miRNA polymorphisms in hepatotoxicity.
机构信息
Department of Genetics, Physic Anthropology & Animal Physiology, University of the Basque Country, UPV/EHU, Leioa, Spain.
Department of Pediatrics, University Hospital Donostia, San Sebastian, Spain.
出版信息
Epigenomics. 2018 Apr 1;10(4):409-417. doi: 10.2217/epi-2017-0138. Epub 2018 Mar 23.
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.
目的
在儿童急性淋巴细胞白血病（ALL）治疗期间，肝毒性是最常见的与药物相关的毒性之一。许多参与肝脏特异性信号通路的基因受到 miRNA 的严格控制，而 miRNA 的功能可以通过 SNP 进行调节。因此，我们假设 miRNA 中的变体可能与药物诱导的肝毒性有关。
方法
我们在 179 名接受同质治疗的 ALL 儿童队列中分析了 206 个 miRNA 中的 213 个 SNP。
结果
在巩固阶段经过错误发现率校正后，miR-1208 中的 rs2648841 是最显著的 SNP，可能通过对其靶基因 DHFR、MTR 和 MTHFR 的影响。
结论
这些结果表明，miRNA 中的 SNP 可能参与了 ALL 儿童化疗的毒性。
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