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2018 Fiscal Year Final Research Report

Development of individualization drug therapy for mycophenolate mofechil focused on the DNA methylation of UGT (UDP- glucuronosyltransferase) 1A8

Research Project

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Project/Area Number 16K08402
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionOkayama University

Principal Investigator

SUNO MANABU  岡山大学, 医歯薬学総合研究科, 准教授 (20621189)

Co-Investigator(Kenkyū-buntansha) 大谷 真二  岡山大学, 大学病院, 助教 (10770779)
永坂 岳司  川崎医科大学, 医学部, 准教授 (30452569)
有吉 範高  岡山大学, 医歯薬学総合研究科, 教授 (00243957)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywordsメチル化DNA / 免疫抑制薬 / ミコフェノール酸 / UGT1A8
Outline of Final Research Achievements

The results in this study revealed that patients with non-methylated DNA sequences in UGT1A8 5' flanking region tended to have lower trough mycophenolic acid blood concentrations. The information on methylation at the UGT1A8 5' franking region was found to be useful for individualisation of mycophenolate mofechil doses and mycophenolic acid plasma concentrations monitoring in clinical settings.
Limitations of this study include, the UGT1A8 expression level evaluation has not been established, and the effect of UGT1A8 expressed in the intestine has not been evaluated. In future, using real-time PCR, we will clarify the difference between UGT1A8 methylation information and UGT1A8 expression level.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

今回の研究により,UGT1A8 5’フランキング領域中-228に非メチル化配列をもつ患者では,ミコフェノール酸トラフ血中濃度が低くなる傾向にあることを明らかにした。これまでUGT1A8の一塩基多型を用いた遺伝子多型別では説明ができなかったミコフェノール酸トラフ血中濃度の個体差を,エピジェネティック解析 を行う,すなわち,UGT1A8 5'フランキング領域におけるメチル化情報を得ることによって患者個々のミコフェノール酸モフェチルの投与量を設定を可能にし,薬剤師が行うミコフェノール酸血中濃度モニタリング時には有用な情報となることを見出した。

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Published: 2020-03-30  

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