Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning City, Guangxi, China.
Hum Genomics. 2021 May 25;15(1):30. doi: 10.1186/s40246-021-00331-6.
UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.
UDP-葡糖醛酸基转移酶（UGTs）是介导人体中最广泛的葡糖醛酸化结合反应的主要 II 相药物代谢酶。UGT1A 家族参与了超过一半的葡糖醛酸化反应。然而，UGT1As 在体内的分布和个体之间的 UGT1As 表达存在显著差异，这些差异与疾病的发生和代谢的差异有关。除了遗传多态性外，人们现在对表观遗传学和非编码 RNA（特别是 miRNA）对这种差异变化的贡献感兴趣。表观遗传学通过 DNA 甲基化和组蛋白修饰来调节 UGT1As 的转录前，而 miRNA 被认为是 UGT1As 转录后调节的关键机制。表观遗传遗传和 miRNA 都参与了 UGT1As 的性别表达和体内分布的差异。此外，生命早期的表观遗传变化已被证明会影响整个生命周期的基因表达。在这里，我们综述和总结了表观遗传学在 UGT1A 家族中的调控作用，并讨论了表观遗传学与 UGT1A 相关疾病和治疗的关系，为未来的研究提供了参考。
