Epigenetics and microRNAs in UGT1As

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.

Automated summary

UDP-glucuronosyltransferases are important drug-metabolizing enzymes in the human body, with UGT1A family being crucial in glucuronidation reactions. Differences in the distribution and expression of UGT1As among individuals contribute to disease occurrence and metabolic variations. Additionally, epigenetics and miRNAs play a role in regulating UGT1As and impacting sex expression and in vivo distribution, with early life epigenetic changes affecting gene expression throughout life.