Research on genomic biomarker exploration on drug-induced liver injury in Japanese, their functional analysis and diagnosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06775
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Saito Yoshiro 国立医薬品食品衛生研究所, 医薬安全科学部, 部長 (50215571)
• Co-Investigator(Kenkyū-buntansha): 荒川 憲昭 国立医薬品食品衛生研究所, 医薬安全科学部, 主任研究官 (60398394)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 薬物性肝障害 / ゲノム

Outline of Final Research Achievements

Drug-induced liver injury is one of the most serious adverse drug reactions that should be avoided because it is one of the most common causes of drug development discontinuation and withdrawal from the market, causes many patients applied to adverse drug reaction relief system, and can lead to death or liver transplantation, such as fulminant hepatic failure. We collected genomic DNA of Japanese patients with drug-induced liver injury and performed HLA analysis and genome-wide association analysis using genetic polymorphism data to search for polymorphisms associated with the onset of drug-induced liver injury. As a result, we found a significantly associated genetic polymorphism in all patients, and significantly related genetic polymorphism and HLA type in patients who were administered Kampo medicine, respectively. We plan to analyze the mechanism of the latter, including the analysis of related herbal medicine components.

Free Research Field

医療系薬学

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、日本人を対象に薬物性肝障害の発症と関連する遺伝子多型候補を明らかにしたものであり、別群試料での検証が必要なものの新規性が高いと考えられる。発症予測マーカーとしての確立後は、当該医薬品の投与前にゲノム診断を行うことにより、発症回避につながることが期待され、予測・予防型の医薬品安全対策に資すると考えられるため、社会的意義も大きいと考える。特にHLA型は、既に臨床検査としての外注による評価が可能なため、臨床応用は容易と考えられる。