Analysis of epigenetic mechanisms on the regulation of drug metabolizing enzymes and its application to personalized drug therapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590451
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: HABANO WATARU 岩手医科大学, 薬学部, 准教授 (50332979)
• Co-Investigator(Renkei-kenkyūsha): SUGAI Tamotsu 岩手医科大学, 医学部, 教授 (20187628)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬物代謝変動 / エピジェネティクス

Outline of Final Research Achievements

We evaluated the biological significance of DNA methylation in the regulation of drug metabolizing enzyme (DME) genes by genome-wide integrative analysis. Among normal livers, 7 DME genes showed significant inverse correlations between DNA methylation and mRNA expression. In hepatoma cells, treatment with a demethylating agent resulted in upregulation of 5 DME genes, which could be explained by DNA methylation status. Tissue-specific and age-dependent expression of UDP-glucuronosyl transferase 1A splicing variants could be explained by DNA methylation status. Interestingly, some DME genes had unique methylation features similar to those observed in tumor-suppressor or housekeeping genes. Analysis of the DNA methylation landscape facilitated elucidation of the role of DNA methylation.

Free Research Field

人体病理学