DNA methylation biomarkers for estimation of the activity of CYP3A4 in human livers

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293121
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyushu University
• Principal Investigator: Ieiri Ichiro 九州大学, 薬学研究科(研究院), 教授 (60253473)
• Co-Investigator(Kenkyū-buntansha): 廣田 豪 九州大学, 薬学研究科(研究院), 助教 (80423573)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬剤反応性 / ゲノム / CYP3A4 / コヒーシンモデル

Outline of Final Research Achievements

CYP3A4 is the major CYP isozyme in adult human liver, small intestine and other extrahepatic tissues.　A wide inter-individual variation exists in levels of expression of CYP3A4. The basis of this variation is not yet understood but may be due to genetic factors. However, the allelic frequencies of SNPs and/or the available functional data indicate a limited role of these variants in the inter-individual variability of CYP3A4 expression and activity. We analyzed the epigenetic mechanisms to regulate the transcription of CYP3A4 gene. Our results showed the relationship between CYP3A4 expression and the status of DNA methylations in human liver, and the conformation around CYP3A locus has the cohesin loop model based on the Gα binding complex. In addition, we established the method to isolate the circulating cells in human blood, and the isolated hepatic cells from peripheral blood showed the expression of human miR-122 which is expressed only in human livers.

Free Research Field

薬物動態学