硫嘌呤药物基因组学在儿科的临床应用

Clinical Application of Thiopurine Pharmacogenomics in Pediatrics.

作者信息

Pavlovic Sonja, Kotur Nikola, Stankovic Biljana, Gasic Vladimir, Lucafo Marianna, Decorti Giuliana, Zukic Branka

机构信息

Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.

Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

出版信息

Curr Drug Metab. 2020;21(1):53-62. doi: 10.2174/1389200221666200303113456.

DOI:10.2174/1389200221666200303113456

PMID:32124692

Abstract

BACKGROUND

Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice.

OBJECTIVE

The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care.

METHODS

We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases.

RESULTS

TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce.

CONCLUSION

Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.

摘要

背景

硫嘌呤类药物用于治疗儿科疾病。这些药物代谢的个体差异极大地影响了硫嘌呤诱导毒性和治疗失败的风险。这些差异是患者基因组、表观基因组和转录组变异的结果。药物基因组学旨在根据患者的特定基因特征实现个体化治疗。通过在儿科临床实践中应用药物基因组学，基于硫嘌呤类药物的治疗方案已经得到改进。

目的

本综述的目的是总结硫嘌呤药物基因组学在患有急性白血病、不同类型自身免疫性和炎性疾病的儿科患者以及移植后护理中的应用。

方法

我们检索了PubMed/Medline数据库，以确定在儿科疾病中具有临床相关性的硫嘌呤药物基因组学标志物。

结果

在儿科护理中进行了硫嘌呤甲基转移酶（TPMT）和NUDT15药物基因组学检测，有助于降低硫嘌呤诱导的毒性。关于许多与优化硫嘌呤治疗相关的新型潜在药物基因组学标志物的数据仍存在争议（inosine triphosphatase，ITPA；ATP结合盒转运体C4，ABCC4；5′-核苷酸酶胞质2型，NT5C2；磷酸核糖焦磷酸合成酶1，PRPS1；谷胱甘肽S-转移酶M1，GSTM1；脂肪量和肥胖相关基因，FTO基因变异）。关于儿科硫嘌呤药物基因组学的大多数证据是通过研究急性淋巴细胞白血病和炎性肠病获得的。对于其他儿科疾病，即急性髓细胞白血病、非霍奇金淋巴瘤、幼年特发性关节炎、特应性皮炎、幼年自身免疫性肝炎和肾移植，数据仍然稀少。