International collaboration on the research of novel urate transporters by leveraging genetic differences between the Japanese and the Czech

2020 Fiscal Year Final Research Report

• Project/Area Number: 18KK0247
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: TAKADA Tappei 東京大学, 医学部附属病院, 講師 (90376468)
• Co-Investigator(Kenkyū-buntansha): 市田 公美 東京薬科大学, 薬学部, 教授 (80183169) ; 松尾 洋孝 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 分子生体制御学, 准教授 (00528292) ; 豊田 優 東京大学, 医学部附属病院, 届出研究員 (80650340)
• Project Period (FY): 2018-10-09 – 2021-03-31
• Keywords: 尿酸 / 遺伝子多型 / トランスポーター / 人種差 / 国際共同研究

Outline of Final Research Achievements

By a series of in vitro experiments and clinical analyses including international collaborations, we revealed that 1) there were clinically-relevant rare dysfunctional variants of ABCG2 in a gout and hyperuricemia cohort, 2) there were novel loci which aggravate asymptomatic hyperuricemia into gout revealed by genome-wide association studies, 3) familial early-onset hyperuricemia and gout associated with dysfunctional variants of ABCG2, 4) there were subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients.

Free Research Field

トランスポーター研究

Academic Significance and Societal Importance of the Research Achievements

本国際共同研究で得られた研究成果は、痛風、高尿酸血症をはじめとするさまざまな尿酸関連疾患の予防・治療戦略の立案に役立つことが期待される。例えば、より精度の高い遺伝子診断による各種疾患のリスク予測などに貢献しうるものであり、今後、応用研究や社会実装も見据えた研究のさらなる発展が期待される。